Quinoline and quinazoline derivatives and drugs containing the same

ABSTRACT

There are provided compounds which can be used in the treatment of diseases mediated by the autophosphorylation of a PDGF receptor, specifically, compounds which can inhibit neointima formation hypertrophy. The compounds are those represented by formula (I) or pharmacologically acceptable salts or solvates thereof:  
                 
 
wherein R 1  and R 2  represent hydrogen, alkyl or the like; R 3 , R 4 , R 5 , and R 6  represent hydrogen, halogen, alkyl, alkoxy or the like; R 11  and R 12  represent hydrogen, alkyl, alkylcarbonyl or the like; and A represents any one of formulae (i) to (x), provided that compounds wherein R 3 , R 4 , R 5  and R 6  represent hydrogen and A represents group (v) wherein u is 0 (zero) and R 19  represents phenyl optionally substituted by halogen, alkyl, or alkoxy are excluded.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to quinoline derivatives and quinazoline derivatives and more particularly to quinoline derivatives and quinazoline derivatives that can be used in the treatment of diseases associated with the autophosphorylation of a PDGF receptor and particularly can inhibit angiostenosis.

2. Background Art

PTCA (percutaneous transluminal coronary angioplasty) is widely adopted as therapy useful for ischemic heart diseases resulting from coronary stenosis. Vascular restenosis, which is observed in a frequency of about 30% within 3 to 6 months after the operation of PTCA, however, has become a serious problem associated with long-term prognosis and medical economy. The restenosis is considered attributable to the fact that vascular smooth muscular cells or fibroblasts of the vascular outer membrane are activated, for example, by platelet activation caused by the tear of vascular tunica intima or media, extension stimulation, and vascular endothelial cell injury at the time of catheter therapy and consequently migrate and proliferate and excessively accumulate at injured vascular sites.

Various growth factors have hitherto been assumed as the vascular smooth muscle cells or fibroblasts activation factors. In particular, since R. Ross et al. have proposed a hypothesis of a injury reaction (N. Engl. J. Med., 295, 369 (1976)), PDGF (platelet-derived growth factor) has drawn attention as one of factors causative of arteriosclerosis and has been also considered as a major factor causative of restenosis from both fundamental and clinical aspects (G. A. A. Ferns et al., Science, 253, 1129 (1991), M. G. Sirois et al., Circulation, 95, 669 (1997), and M. Ueda et al., Am. J. Pathol., 149, 831 (1996) etc.).

PDGF-R (PDGF receptor) autophosphorylation inhibitory compounds (WO 97/17329 and The FASEB Journal, Vol. 11, pp. 1119-1126 (1997)) have been reported up to now.

For PDGF receptor autophosphorylation inhibitory compounds which have been reported, however, the selectivity for VEGF receptors (such as KDR) and c-kit (SCF receptors) belonging to the PDGF receptor family has not been discussed.

VEGF is one of major growth factors of vascular endothelial cells (EC), and VEGF receptor inhibitory compounds possibly inhibit the regeneration of EC in injured blood vessels to promote the formation of thrombus and to accelerate angiostenosis.

Further, SCF is a growth factor involved in the upstream of hematopoietic system and the movement of intestinal tracts, and substances that inhibit receptors of SCF possibly induce hematopoietic failure and intestinal tract movement failure.

For these reasons, compounds that can selectively inhibit PDGF receptors for c-kit, KDR, and the like are family are expected as anti-restenosis agents that have no significant side effect.

Although various restenosis inhibitors have been developed up to now, any pharmaceutical compound having potent angiostenosis inhibitory activity has not yet been developed.

SUMMARY OF THE INVENTION

The present inventors have now found out compounds having PDGF receptor autophosphorylation inhibitory activity.

The present inventors have also found out compounds inhibiting angiostenosis in rat carotid balloon injury models and porcine coronary balloon injury models.

The present inventors have further found out compounds having potent PDGF receptor autophosphorylation inhibitory activity and having low VEGF receptor autophosphorylation inhibitory activity.

The present inventors have further found out compounds having PDGF receptor autophosphorylation inhibitory activity and having low c-kit autophosphorylation inhibitory activity.

An object of the present invention is to provide compounds that can be used in the treatment of diseases mediated by the autophosphorylation of PDGF receptors, particularly compounds having inhibitory activity against angiostenosis.

Another object of the present invention is to provide compounds that can be used in the treatment of diseases mediated by the autophosphorylation of PDGF receptors and have a low level of side effects attributable to c-kit autophosphorylation inhibitory activity.

According to the present invention, there is provided a compound represented by formula (I) or a pharmacologically acceptable salt or solvate thereof:

wherein

X and Z, which may be the same or different, represent CH or N;

R¹ and R², which may be the same or different, represent a hydrogen atom or C₁₋₄ alkoxy optionally substituted by a halogen atom;

R³, R⁴, R⁵, and R⁶, which may be the same or different, represent a hydrogen atom; a halogen atom; C₁₋₄ alkyl optionally substituted by a halogen atom; C₁₋₄ alkoxy optionally substituted by a halogen atom; nitro; amino; or morpholyl;

A represents a group selected from the group consisting of formulae (i) to (x), wherein R¹¹ and R¹², which may be the same or different, represent a hydrogen atom, C₁₋₄ alkyl optionally substituted by a halogen atom, or C₁₋₄ alkylcarbonyl optionally substituted by a halogen atom;

provided that compounds wherein R³, R⁴, R¹ and R⁶ represent a hydrogen atom and A represents group (v) wherein u is 0 (zero) and R¹⁹ represents phenyl optionally substituted by a halogen atom, C₁₋₄ alkyl, or C₁₋₄ alkoxy are excluded:

wherein

i is an integer of 0 to 10,

R¹³ and R¹⁴, which may be the same or different, represent a hydrogen atom; C₁₋₆ alkyl optionally substituted by a halogen atom; or phenyl optionally substituted by a halogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom,

R¹³ and R¹⁴ may form a five- to seven-membered saturated or unsaturated heterocyclic ring optionally containing one or more additional hetero-atoms together with the nitrogen atom to which they are attached, and this heterocyclic ring is optionally substituted by a halogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom, or, R¹³ or R¹⁴ may form C₁₋₄ alkylene optionally substituted by a halogen atom together with R¹²;

wherein

j is an integer of 0 to 3,

k is an integer of 0 to 3, provided that

both j and k are not 0 (zero),

m is an integer of 0 to 2,

carbon atoms in the following

are optionally substituted by one or more C₁₋₄ alkyl groups, which may be the same or different, optionally substituted by a halogen atom, and

R¹⁵ represents a hydrogen atom; cyclic C₃₋₇ alkyl optionally substituted by a halogen atom; phenyl optionally substituted by C₁₋₆ alkyl or a halogen atom; or C₁₋₄ alkoxycarbonyl;

wherein

n is 0 (zero) or 1,

p is an integer of 0 to 10, and

R¹⁶ and R¹⁷, which may be the same or different, represent a hydrogen atom; C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₄ alkylcarbonyl optionally substituted by a halogen atom; cyclic C₃₋₇ alkyl optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom; or phenyl optionally substituted by a halogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom, or

R¹⁶ and R¹⁷ may form a five- to seven-membered saturated or unsaturated heterocyclic ring optionally containing one or more additional hetero-atoms together with the nitrogen atom to which they are attached, this heterocyclic ring is optionally condensed with another one or two carbocyclic or heterocyclic ring to form a ten- to twelve-membered saturated or unsaturated bicyclic carbocyclic ring or heterocyclic ring or a ten- to fifteen-membered saturated or unsaturated tricyclic carbocyclic ring or heterocyclic ring, and these heterocyclic rings are optionally substituted by an oxygen atom or C₁₋₄ alkyl optionally substituted by a halogen atom;

wherein

q is 0 (zero) or 1,

r is an integer of 0 to 3,

s is an integer of 0 to 3, provided that

both r and s are not 0 (zero),

t is an integer of 0 to 2,

carbon atoms in the following

are optionally substituted by one or more C₁₋₄ alkyl groups, which may be the same or different, and

R¹⁸ represents a hydrogen atom; phenyl optionally substituted by a halogen atom or C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₄ alkoxycarbonyl optionally substituted by a halogen atom;

wherein

u is 0 (zero) or 1,

R¹⁹ represents

(1) phenyl which is optionally substituted by C₁₋₁₀ alkyl optionally substituted by a halogen atom; C₁₋₁₀ alkoxy optionally substituted by a halogen atom; —NR³¹R³² wherein R³¹ and R³², which may be the same or different, represent a hydrogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,

(2) phenoxy of which the phenyl portion is optionally substituted by C₁₋₁₀ alkyl optionally substituted by a halogen atom; C₁₋₁₀ alkoxy optionally substituted by a halogen atom; —NR³¹R³² wherein R³¹ and R³² are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,

(3) cyclic C₃₋₇ alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; cyclic C₃₋₇ alkyl optionally substituted by a halogen atom; or a halogen atom,

(4) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom,

(5) C₁₋₁₆ alkyl,

(6) C₂₋₆ alkenyl, or

(7) C₂₋₆ alkynyl,

wherein (5) C₁₋₁₆ alkyl, (6) C₂₋₆ alkenyl, and (7) C₂₋₆ alkynyl are optionally substituted by one or more of the following groups:

(a) phenyl optionally substituted by C₁₋₁₀ alkyl optionally substituted by a halogen atom; C₁₋₁₀ alkoxy optionally substituted by a halogen atom; —NR³¹R³² wherein R³¹ and R³² are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,

(b) phenoxy of which the phenyl portion is optionally substituted by C₁₋₁₀ alkyl optionally substituted by a halogen atom; C₁₋₁₀ alkoxy optionally substituted by a halogen atom; —NR³¹R³² wherein R³¹ and R³² are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,

(c) phenylthio of which the phenyl portion is optionally substituted by C₁₋₁₀ alkyl optionally substituted by a halogen atom; C₁₋₁₀ alkoxy optionally substituted by a halogen atom; —NR³¹R³² wherein R³¹ and R³² are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,

(d) —NR³³R³⁴ wherein R³³ and R³⁴ are as defined in R¹³ and R¹⁴,

(e) cyclic C₃₋₇ alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; or a halogen atom,

(f) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom,

(g) naphthyl,

(h) cyano,

(i) C₁₋₄ alkylthio optionally substituted by a halogen atom,

(j) a halogen atom, or

(k) alkoxycarbonyl optionally substituted by a halogen atom;

wherein

R²⁰ represents

(1) phenyl optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁵R³⁶ wherein R³⁵ and R³⁶, which may be the same or different, represent a hydrogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,

(2) cyclic C₃₋₇ alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom,

(3) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom,

(4) C₁₋₂₀ alkyl,

(5) C₂₋₆ alkenyl, or

(6) C₂₋₆ alkynyl, and

wherein (4) C₁₋₂₀ alkyl, (5) C₂₋₆ alkenyl, and (6) C₂₋₆ alkynyl are optionally substituted by one or more of the following groups:

(a) phenyl optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁵R³⁶ wherein R³⁵ and R³⁶ are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,

(b) phenoxy of which the phenyl portion is optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁵R³⁶ wherein R³⁵ and R³⁶ are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,

(c) phenylthio of which the phenyl portion is optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁵R³⁶ wherein R³⁵ and R³⁶ are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,

(d) —NR³⁷R³⁸ wherein R³⁷ and R³⁸ are as defined in R¹³ and R¹⁴,

(e) cyclic C₃₋₇ alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom,

(f) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom,

(g) naphthyl, or

(h) cyano;

wherein

v is an integer of 0 to 2,

R²¹ represents

(1) phenyl optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁹R⁴⁰ wherein R³⁹ and R⁴⁰, which may be the same or different, represent a hydrogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,

(2) cyclic C₃₋₇ alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom,

(3) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom,

(4) C₁₋₂₀ alkyl,

(5) C₂₋₆ alkenyl, or

(6) C₂₋₆ alkynyl, and

wherein (4) C₁₋₂₀ alkyl, (5) C₂₋₆ alkenyl, and (6) C₂₋₆ alkynyl are optionally substituted by one or more of the following groups:

(a) phenyl optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁹R⁴⁰ wherein R³⁹ and R⁴⁰ are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,

(b) phenoxy of which the phenyl portion is optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁹R⁴⁰ wherein R³⁹ and R⁴⁰ are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,

(c) phenylthio of which the phenyl portion is optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁹R⁴⁰ wherein R³⁹ and R⁴⁰ are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,

(d) —NR⁴¹R⁴² wherein R⁴¹ and R⁴² are as defined in R¹³ and R¹⁴,

(e) cyclic C₃₋₇ alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom,

(f) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom,

(g) naphthyl, or

(h) cyano;

wherein

w is an integer of 1 to 4,

L represents —O—, —S(═O)y-, wherein y is an integer of 0 to 2, or —N(—R¹¹)—,

M represents —O—, —C(═O)—O—, —S(═O)z-, wherein z is an integer of 0 to 2, —N(—R¹²)—, —C(═O)—N(—R¹²)—, or —C(═O)—,

R²² represents a hydrogen atom; C₁₋₄ alkyl optionally substituted by a halogen atom; or phenyl optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, C₁₋₄ alkoxy optionally substituted by a halogen atom, nitro, amino, or a halogen atom,

when M represents —N(—R¹²)— or —C(═O)—N(—R¹²)—, R²² and R¹² may form a five- to seven-membered saturated or unsaturated heterocyclic ring optionally containing one or more additional hetero-atoms together with the nitrogen atom to which they are attached, this heterocyclic ring is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring, and these heterocyclic rings are optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom; phenyl; benzyl; or piperidine; —OR²³  (ix) wherein R²³ represents a hydrogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom; and —NR²⁴R²⁵  (x) wherein R²⁴ and R²⁵, which may be the same or different, represent a hydrogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom.

The compounds according to the present invention are useful for the treatment of diseases mediated by the autophosphorylation of PDGF receptors.

DETAILED DESCRIPTION OF THE INVENTION

Compound

The terms “alkyl,” “alkoxy,” “alkenyl,” and “alkynyl” as used herein as a group or a part of a group respectively mean straight chain or branched chain alkyl, alkoxy, alkenyl, and alkynyl.

C₁₋₆ alkyl is preferably C₁₋₄ alkyl.

C₁₋₁₀ alkyl is preferably C₁₋₈ alkyl.

C₁₋₁₆ alkyl is preferably C₁₋₁₃ alkyl.

C₁₋₂₀ alkyl is preferably C₁₋₁₈ alkyl.

C₁₋₆ alkoxy is preferably C₁₋₄ alkoxy.

C₁₋₁₀ alkoxy is preferably C₁₋₈ alkoxy.

C₂₋₆ alkenyl is preferably C₂₋₄ alkenyl.

C₂₋₆ alkynyl is preferably C₂₋₄ alkynyl.

Examples of C₁₋₆ alkyl include methyl, ethyl, n-propyl, isopropyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, and n-hexyl.

Examples of C₁₋₆ alkoxy include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, s-butoxy, and t-butoxy.

Examples of C₂₋₆ alkenyl include allyl, butenyl, pentenyl, and hexenyl.

Examples of C₂₋₆ alkynyl include 2-propynyl, butynyl, pentynyl, and hexynyl.

The expression “alkyl optionally substituted by” as used herein means alkyl, of which one or more hydrogen atoms are substituted by one or more substituents which may be the same or different, or unsubstituted alkyl. It will be understood by a person skilled in the art that the maximum number of the substituents can be determined depending upon the number of substitutable hydrogen atoms on the alkyl group. This will apply to groups having substituents other than alkyl.

The term “halogen atom” as used herein means a fluorine, chlorine, bromine, or iodine atom.

The saturated or unsaturated five- to seven-membered heterocyclic ring contains one or more hetero-atoms selected from oxygen, nitrogen, and sulfur atoms. Examples of the saturated or unsaturated five- to seven-membered heterocyclic group include pyridyl, piperidino, piperazino, morpholino, imidazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, pyrrolidinyl, and pyrazolyl.

The five- to seven-membered saturated or unsaturated heterocyclic group may be condensed with another saturated or unsaturated carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic ring or a ten- to fifteen-membered tricyclic ring. Condensed bicyclic groups include indanyl, quinolyl, and quinazolinyl. Condensed tricyclic groups include phenythiazyl, phenoxazyl, and dihydrodibenzoazepinyl.

Cyclic C₃₋₇ alkyl may be condensed with another saturated or unsaturated carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring. Condensed bicyclic groups include indanyl, quinolyl, and quinazolinyl.

In group (i), i is preferably an integer of 0 to 4, more preferably 1 to 3.

An example of preferred group (i) is a group wherein i is an integer of 1 to 3, R¹³ and R¹⁴, which may be the same or different, represent C₁₋₄ alkyl or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl together with the nitrogen atom, to which they are attached.

In group (ii), j is preferably an integer of 1 or 2. k is preferably an integer of 1 or 2. m is preferably an integer of 1 or 2.

An example of preferred group (ii) is a group wherein j is 1 or 2, k is 1 or 2, m is 1 or 2, and R¹⁵ represents optionally substituted phenyl.

In group (iii), p is preferably an integer of 0 to 3.

An example of preferred group (iii) is a group wherein n is 0 (zero), p is an integer of 1 to 3, and R¹⁶ and R¹⁷, which may be the same or different, represent C₁₋₄ alkyl or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl or an oxygen atom together with the nitrogen atom, to which they are attached.

Another example of preferred group (iii) is a group wherein n is 1 and p is 0 (zero).

In group (iv), r is preferably an integer of 1 or 2. s is preferably an integer of 1 or 2. t is preferably an integer of 0 or 1.

An example of preferred group (iv) is a group wherein q is 0 (zero), r is 1 or 2, s is 1 or 2, t is 1 or 2, and R¹⁸ represents optionally substituted phenyl.

In group (v), the phenyl and phenoxy groups presented by R¹⁹ are optionally substituted by C₆₋₁₀ alkyl or C₆₋₁₀ alkoxy, preferably C₆₋₈ alkyl or C₆₋₈ alkoxy.

In group (v), the alkyl, alkenyl, and alkynyl groups presented by R¹⁹ are optionally substituted by phenyl, phenoxy, or phenylthio, and this phenyl, phenoxy, or phenylthio group is optionally substituted by C₆₋₁₀ alkyl or C₆₋₁₀ alkoxy, preferably C₆₋₈ alkyl or C₆₋₈ alkoxy.

An example of preferred group (v) is a group wherein u is 1 and R¹⁹ represents C₁₋₄ alkyl substituted by optionally substituted phenyl.

An example of preferred group (vi) is a group wherein R²⁰ represents optionally substituted phenyl or C₁₋₆ alkyl optionally substituted by optionally substituted phenyl.

In group (viii), w is preferably an integer of 1 to 3.

When L represents —O—, preferably, M represents —O—, —C(═O)—O—, —N(—R¹²)—, —C(═O)—N(—R¹²)—, or —C(═O)—. When L represents —S(═O)y-, preferably, M represents —O—. When L represents —N(—R¹¹)—, preferably, M represents —O—.

An example of preferred group (viii) is a group wherein w is an integer of 1 to 3, L represents —O—, M represents —O— or —C(═O)—O—, and R²² represents optionally substituted phenyl.

Examples of preferred compounds represented by formula (I) according to the present invention include the following compounds:

compounds wherein X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy and at least one of R³, R⁴, R⁵ and R⁶ represents a group other than a hydrogen atom;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, R³ represents a group other than a hydrogen atom, and R⁴, R⁵, and R⁶ represent a hydrogen atom;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, A represents group (i), wherein i is an integer of 1 to 3, and R¹³ and R¹⁴, which may be the same or different, represent C₁₋₄ alkyl or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl together with the nitrogen atom, to which they are attached and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, R³, R⁴, R⁵ and R⁶ represent a hydrogen atom, A represents group (i), wherein i is an integer of 1 to 3, and R¹³ and R¹⁴, which may be the same or different, represent C₁₋₄ alkyl or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl together with the nitrogen atom to which they are attached and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, R³ represents a group other than a hydrogen atom, R⁴, R⁵ and R⁶ represent a hydrogen atom, A represents group (i) wherein i is an integer of 1 to 3, and R¹³ and R¹⁴, which may be the same or different, represent C₁₋₄ alkyl or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl together with the nitrogen atom, to which they are attached, and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, R³ represents nitro, R⁴, R⁵, and R⁶ represent a hydrogen atom, A represents group (i) wherein i is an integer of 1 to 3, and R¹³ and R¹⁴, which may be the same or different, represent C₁₋₄ alkyl or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl together with the nitrogen atom, to which they are attached, and, more preferably, X represents CH or N and Z represents CH;

compounds wherein X represents N, Z represents CH, R¹ and R² represent C₁₋₄ alkoxy, R³ represents nitro, R⁴, R⁵, and R⁶ represent a hydrogen atom, A represents group (i) wherein i is 2, and R¹³ and R⁴, which may be the same or different, represent C₂₋₃ alkyl or may form a six-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl together with the nitrogen atom, to which they are attached;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, A represents group (ii) wherein j is 1 or 2, k is 1 or 2, m is 1 or 2, and R¹⁵ represents optionally substituted phenyl and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, R³, R⁴, R⁵, and R⁶ represent a hydrogen atom, A represents group (ii) wherein j is 1 or 2, k is 1 or 2, m is 1 or 2, and R¹⁵ represents optionally substituted phenyl;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, R³ represents a group other than a hydrogen atom, R⁴, R⁵, and R⁶ represent a hydrogen atom, A represents group (ii) wherein j is 1 or 2, k is 1 or 2, m is 1 or 2, and R¹⁵ represents optionally substituted phenyl and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, A represents group (iii) wherein n is 0 (zero), p is an integer of 1 to 3, and R¹⁶ and R¹⁷, which may be the same or different, represent C₁₋₄ alkyl or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl or an oxygen atom together with the nitrogen atom, to which they are attached, and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, R³, R⁴, R⁵, and R⁶ represent a hydrogen atom, A represents group (iii) wherein n is 0 (zero), p is an integer of 1 to 3, and R¹⁶ and R¹⁷, which may be the same or different, represent C₁₋₄ alkyl or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl or an oxygen atom together with the nitrogen atom, to which they are attached, and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, R³ represents a group other than a hydrogen atom, R⁴, R⁵, and R⁶ represent a hydrogen atom, A represents group (iii) wherein n is 0 (zero), p is an integer of 1 to 3, and R¹⁶ and R¹⁷, which may be the same or different, represent C₁₋₄ alkyl or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl or an oxygen atom together with the nitrogen atom, to which they are attached, and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, A represents group (iv) wherein q is 0 (zero), r is 1 or 2, s is 1 or 2, t is 1 or 2, and R¹⁸ represents optionally substituted phenyl, and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, R³, R⁴, R⁵ and R⁶ represent a hydrogen atom, and A represents group (iv) wherein q is 0 (zero), r is 1 or 2, s is 1 or 2, t is 1 or 2, and R¹⁸ represents optionally substituted phenyl;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, R³ represents a group other than a hydrogen atom, R¹, R⁵, and R⁶ represent a hydrogen atom, and A represents group (iv) wherein q is 0 (zero), r is 1 or 2, s is 1 or 2, t is 1 or 2, and R¹⁸ represents optionally substituted phenyl, and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (v), wherein u is 1, and R¹⁹ represents optionally substituted phenyl, or C₁₋₄ alkyl substituted by optionally substituted phenyl, and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, R³, R⁴, R⁵, and R⁶ represent a hydrogen atom, A represents group (v) wherein u is 1, R¹⁹ represents optionally substituted phenyl, or C₁₋₄ alkyl substituted by optionally substituted phenyl;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, R⁵ represents a group other than a hydrogen atom, R³, R⁴, and R⁶ represent a hydrogen atom, and A represents group (v) wherein u is 1, R¹⁹ represents optionally substituted phenyl, or C₁₋₄ alkyl substituted by optionally substituted phenyl, and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (vi) wherein R²⁰ represents optionally substituted phenyl or C₁₋₆ alkyl optionally substituted by optionally substituted phenyl, and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (vii) wherein R²¹ represents optionally substituted phenyl, or C₁₋₆ alkyl optionally substituted by optionally substituted phenyl, and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (viii) wherein w is an integer of 1 to 3, L represents —O—, M represents —O— or —C(═O)—O—, R²² represents optionally substituted phenyl, and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (viii) wherein, when L represents —O—, M represents —O—, —C(═O)—O—, —N(—R¹²)—, —C(═O)—N(—R¹²)—, or —C(═O)—; when L represents —S(═O)y-, M represents —O—; and when L represents —N(—R¹¹)—, M represents —O—, and, more preferably, X represents CH or N and Z represents CH;

compounds wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (iii), wherein n is 1 and p is 0 (zero), and, more preferably, X represents CH or N and Z represents CH; and

compounds wherein R¹ and R² represent C₁₋₄ alkoxy, R³ represents morpholyl, R⁴, R⁵, and R⁶ represent a hydrogen atom, and A represents group (x), and, more preferably, X represents CH or N and Z represents CH.

Examples of particularly preferred compounds according to the present invention include compounds described in Examples 1 to 1209.

In addition to the compounds described in Examples 1 to 1209, the following compounds may be included in examples of particularly preferred compounds according to the present invention:

-   N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}-N-(4-piperidinobutyl)urea; -   N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}-N-(3-piperidinopropyl)urea; -   N-[4-(diethylamino)butyl]-N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}urea; -   N-[3-(diethylamino)propyl]-N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}urea; -   N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-(4-methylpiperazino)urea;     and -   N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N-(4-methylpiperazino)urea.

Examples of more preferred compounds according to the present invention are the following compounds:

-   N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}-N′-(2-piperidinoethyl)urea;     and -   N-[2-(diethylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}urea.

One or more enantiomeric carbon atoms, which form enantiomer configuration, may exist in the compounds represented by formula (I). The compounds represented by formula (I) include all enantiomers.

Pharmacologically acceptable salts of the compounds represented by formula (I) include acid addition salts. Acid addition salts include: salts with inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid, and nitric acid; or organic acids such as maleic acid, fumaric acid, malic acid, oxalic acid, tartaric acid, succinic acid, citric acid, acetic acid, lactic acid, methanesulfonic acid, and p-toluenesulfonic acid.

Pharmacologically acceptable solvates of the compounds represented by formula (I) include hydrates and ethanolates.

Production Process of Compounds

(1) Compounds represented by formula (I), wherein A represents groups (i), (ii), (xi), and (x), may be produced, for example, according to scheme 1 and scheme 2.

Starting compounds necessary for the synthesis of the compounds according to the present invention are commercially available or can be easily produced by a conventional method.

Quinolone derivatives as an intermediate may be synthesized according to the method described, for example, in WO 97/17329. Further, 4-chloroquinoline derivatives may be synthesized by a conventional method described, for example, in Org. Synth. Col., Vol. 3, 272 (1955), Acta Chim. Hung., 112, 241 (1983) or WO 98/47873. Further, 4-chloroquinazoline derivatives may be synthesized by a conventional method described, for example, in J. Am. Chem. Soc., 68, 1299 (1946), J. Am. Chem. Soc., 68, 1305 (1946) or Dai-Yukikagaku, supervised by Kotake, Vol. 17, p. 150, Asakura Publishing Co., Ltd., 1967.

4-(Nitrophenoxy)quinoline derivatives or corresponding quinazoline derivatives may be synthesized by reacting nitrophenol with a 4-chloroquinoline derivative or a corresponding quinazoline derivative in the presence or absence of a suitable solvent. 4-(Aminophenoxy)quinoline derivatives or corresponding quinazoline derivatives may be synthesized by stirring a 4-(nitrophenoxy)quinoline derivative or a corresponding quinazoline derivative in a suitable solvent, for example, N,N-dimethylformamide, in the presence of a catalyst, for example, palladium hydroxide-carbon or palladium-carbon) in a hydrogen atmosphere. Alternatively, 4-(aminophenoxy)quinoline derivatives or corresponding quinazoline derivatives may be sythesized by reacting an aminophenol derivative with a 4-chloroquinoline derivative or a corresponding quinazoline derivative in the presence of a base, for example, sodium hydride.

A substituent can be introduced into R¹¹ by reacting a 4-(aminophenoxy)quinoline derivative or a corresponding quinazoline derivative with an acid chloride or an acid anhydride in the presence of a base and then reducing the reaction product with lithium aluminum hydride or the like (step 1A).

Alternatively, a substituent can be introduced into R¹¹ by reacting a 4-(aminophenoxy)quinoline derivative or a corresponding quinazoline derivative with an aldehyde or a ketone to form an imine compound and then reducing the imine compound with sodium cyanoborohydride or the like (step 1B).

Compounds represented by formula (I) may be produced by reacting a derivative having a substituent at R¹¹ with an isocyanate derivative (O═C═N—R⁵¹ wherein R⁵¹ represents a portion of groups (i) and (ii) not having a urea portion according to a conventional method (step 2) and, if necessary, reacting the reaction product with a suitable alkylating agent (R¹²Hal) in the presence of a base, for example, sodium hydride (step 3).

R¹¹ and R¹² may also be introduced by reacting a urea derivative, wherein R¹⁰ and/or R¹¹ represent a hydrogen atom, with a suitable alkylating agent (R¹¹Hal or R¹²Hal) in the presence of a base, for example, sodium hydride (steps 5 and 7).

Urea derivatives, wherein R¹¹ and/or R¹² represent a hydrogen atom, may be produced by reacting a 4-(aminophenoxy)quinoline derivative or a corresponding quinazoline derivative produced in scheme 1 with an isocyanate derivative according to a conventional method, or by adding triphosgene in the presence of a base, for example, triethylamine and then reacting the mixture with a suitable alkylamine (R⁵¹NH₂ or R¹¹R⁵¹NH) (steps 4 and 6).

(2) Compounds represented by formula (I), wherein A represents groups (iii), (iv), and (v), may be produced, for example, according to scheme 3.

A substituent can be introduced into R¹¹ by reacting a 4-(aminophenoxy)quinoline derivative or a corresponding quinazoline derivative with an acid chloride or an acid anhydride in the presence of a base and then reducing the reaction product with lithium aluminum hydride or the like (step 1A).

Alternatively, a substituent can be introduced into R¹¹ by reacting a 4-(aminophenoxy)quinoline derivative or a corresponding quinazoline derivative with an aldehyde or a ketone to form an imine derivative and then reducing the imine derivative with sodium cyanoborohydride or the like (step 1B).

Compounds represented by formula (I) may be produced by reacting a derivative having a substituent at R¹¹ with an isothiocyanate derivative, (S═C═N—R⁵² wherein R⁵² represents a portion of groups (iii), (iv), and (v), not having a thiourea portion according to a conventional method (step 2) and, if necessary, reacting the reaction product with a suitable alkylating agent (R¹²Hal) in the presence of a base, for example, sodium hydride (step 3).

R¹¹ and R¹² may also be introduced by reacting a thiourea derivative, wherein R¹¹ and/or R¹² represent a hydrogen atom, with a suitable alkylating agent (R¹¹Hal or R¹²Hal) in the presence of a base, for example, sodium hydride (steps 5 and 7).

Thiourea derivatives, wherein R¹¹ and/or R¹² represent a hydrogen atom, may be produced by reacting a 4-(aminophenoxy)quinoline derivative or a corresponding quinazoline derivative produced in scheme 1 with an isothiocyanate derivative (S═C═N—R⁵²) according to a conventional method, or by adding thiophosgene in the presence of a base, for example, triethylamine and then reacting the mixture with a suitable alkylamine (R⁵²NH₂ or R¹¹R⁵²NH) (steps 4 and 6).

(3) Compounds represented by formula (I), wherein A represents group (vi), may be produced, for example, according to scheme 4.

Urethane derivatives, wherein R¹¹ and/or R¹² represent a hydrogen atom, may be produced according to a conventional method by adding triphosgene to a 4-(aminophenoxy)quinoline derivative or a corresponding quinazoline derivative produced according to scheme 1 in the presence of a base, for example, triethylamine and then reacting the mixture with a suitable alcohol (R²⁰OH). R¹¹ may be introduced by reacting a urethane derivative, wherein R¹¹ represents a hydrogen atom, with a suitable alkylating agent (R¹¹Hal) in the presence of a base, for example, sodium hydride.

(4) Compounds represented by formula (I), wherein A represents group (vii), may be produced, for example, according to scheme 5.

Thiocarbamate derivatives, wherein R¹¹ and/or R¹² represent a hydrogen atom (v=0), may be produced by adding triphosgene to a 4-(aminophenoxy)quinoline derivative or a corresponding quinazoline derivative produced in scheme 1 in the presence of a base, for example, triethylamine according to a conventional method and then reacting the mixture with a suitable thiol (R²¹SH). R¹¹ may be introduced by reacting a thiocarbamate derivative, wherein R¹¹ represents a hydrogen atom, with a suitable alkylating agent (R¹¹Hal) in the presence of a base, for example, sodium hydride.

Oxidation derivatives (v=1) may be produced by oxidizing the thiocarbamate derivative with an oxidizing agent such as m-chloroperbenzoic acid. Further, oxidation derivatives (v=2) may be produced by oxidizing a thiocarbamate derivative with an oxidizing agent such as potassium permanganate or oxone.

(5) Compounds represented by formula (I), wherein A represents groups (viii) and (ix), may be produced, for example, according to schemes 6, 7, and 8.

4-(Alkyloxyphenoxy)quinoline derivatives or corresponding quinazoline derivatives, or 4-(acyloxyphenoxy) quinoline derivatives or corresponding quinazoline derivatives may be synthesized by reacting a 4-alkyloxyphenol derivative or a 4-acyloxyphenol derivative with a 4-chloroquinoline derivative or a corresponding quinazoline derivative in the presence or absence of a suitable solvent (scheme 6-1). In the scheme, D represents —(CH₂)w-M-R²⁰.

4-(Benzyloxyphenoxy)quinoline derivatives or corresponding quinazoline derivatives, or 4-(benzoyloxyphenoxy)quinoline derivatives or corresponding quinazoline derivatives may be synthesized by reacting a 4-benzyloxyphenol derivative or a 4-benzoyloxyphenol derivative with a 4-chloroquinoline derivative or a corresponding quinazoline derivative in the presence or absence of a suitable solvent (scheme 6-1).

4-(Hydroxyphenoxy)quinoline derivatives or corresponding quinazoline derivatives may be synthesized by deprotecting a 4-(benzyloxyphenoxy)quinoline derivative or a corresponding quinazoline derivative in a suitable solvent, for example, N,N-dimethylformamide, in the presence of a catalyst, for example, palladium hydroxide-carbon or palladium-carbon in a hydrogen atmosphere. 4-(Hydroxyphenoxy)quinoline derivatives or corresponding quinazoline derivatives may also be synthesized by deprotecting the benzoyl group in the 4-(benzoyloxyphenoxy)quinoline derivative or corresponding quinazoline derivative under basic conditions, for example, using sodium hydroxide.

Carboxylic acid compound (1) is produced by reacting a 4-(hydroxyphenoxy)quinoline derivative or a corresponding quinazoline derivative with a ω-halogenated alkyl carboxylic acid ester under basic conditions, for example, using sodium hydride and then deprotecting the ester under basic conditions, for example, using sodium hydroxide. Amide derivative (2) may be produced by reacting carboxylic acid compound (1) with an amine in the presence of a coupling reagent, for example, N,N′-dicyclohexylcarbodiimide. Subsequently, reduced derivative (3) may be produced by reducing amide derivative (2) with diborane, lithium aluminum hydride or the like (scheme 6-2).

S-Alkyl-substituted phenols may be produced by reacting a 4-hydroxythiophenol derivative with a suitable alkyl halide derivative in the presence or absence of a suitable solvent under basic conditions, for example, using potassium carbonate. Thio derivatives may be synthesized by reacting the S-alkyl-substituted phenol with a 4-chloroquinoline derivative or a corresponding quinazoline derivative.

Sulfoxide derivatives may be produced by oxidizing the thio derivative with an oxidizing agent such as m-chloroperbenzoic acid. Sulfone derivatives may be produced by oxidizing the thio derivative with an oxidizing agent such as potassium permanganate or oxone, or by oxidizing the sulfoxide derivative with an oxidizing agent such as potassium permanganate or oxone.

A reduced derivative may be produced by reacting a fatty acid with a 4-(aminophenoxy)quinoline derivative or a corresponding quinazoline derivative produced by a conventional method in the presence of a coupling reagent to give an amide derivative and reducing the amide derivative with diborane, lithium aluminum hydride or the like. R¹¹ may be introduced by reacting a reduced derivative, wherein R¹¹ represents a hydrogen atom, with a suitable alkylating agent (R¹¹Hal) in the presence of a base, for example, sodium hydride. Alternatively, R¹¹ may be introduced by reacting an amide derivative, wherein R¹¹ represents a hydrogen atom, with a suitable alkylating agent (R¹¹Hal) in the presence of a base, for example, sodium hydride. Further, a reduced derivative having a substituent at R¹¹ may be produced by reducing the derivative with diborane, lithium aluminum hydride or the like.

Use of Compounds

The compounds according to the present invention inhibit, in vitro, PDGF-R autophosphorylation and the growth and migration of vascular smooth muscle cells induced by PDGF stimulation (see Pharmacological Test Examples 1 and 2). The autophosphorylation of PDGF receptors mediates diseases, for example, ischemic diseases involving blood vessel occlusion or angiostenosis induced by angiopathy, ischemic diseases involving blood vessel occlusion or angiostenosis induced by vascular autotransplantation or allotransplantation, and diseases involving cell proliferation and organ fibrosis induced by PDGF, for example, chronic rheumatism, PDGF-dependent tumors such as glioma, cirrhosis, pulmonary fibrosis, and occlusion of arteriovenous shunt resulting, for example, from dialysis of patients suffering from renal failure (Gordon A. A. Ferns et al., Science, Vol. 253, pp 1129-1132 (1991), Martin G Sirois et al., Circulation, Vol. 95, No. 3, pp 669-675 (1997), Marukka Myllarniemi et al., The FASEB Journal, Vol. 11, pp 1119-1126 (1997), H. Ohnishi et al., Life Science, Vol. 28, pp 1641-1646 (1981), J. Gastroenterol. Vol. 32, pp 496-501 (1997), Toxicol. Appl. Pharmacol. Vol. 149, pp 120-126 (1998), and Am. J. Pathol. Vol. 148, pp 785-800 (1996)). Further, the compounds according to the present invention have low VEGF-R inhibitory activity (Pharmacological Test Example 5). Compounds, which do not inhibit VEGF-R, are expected not to accelerate angiostenosis. Furthermore, the compounds according to the present invention inhibit, in vivo, neointima formation hypertrophy of injured blood vessels (Pharmacological Test Examples 4 and 6). Therefore, the compounds according to the present invention can be used in the treatment of diseases mediated by the autophosphorylation of PDGF receptors, particularly ischemic diseases involving blood vessel occlusion/angiostenosis induced by blood vessel injury or vascular autotransplantation or allotransplantation.

The compounds according to the present invention have low c-kit autophosphorylation inhibitory activity. The c-kit autophosphorylation inhibitory activity crucially affects hematopoiesis and intestinal tract movements (Experimental Medicine, Vol. 11, No. 13, pp 42-53). Therefore, the present invention can provide compounds which do not cause any significant side effect attributable to c-kit autophosphorylation inhibitory activity.

Pharmaceutical compositions comprising compounds of the present invention as an active ingredient can be administered to human and non-human animals orally or parenterally by administration routes, for example, intravenous administration, intramuscular administration, subcutaneous administration, rectal administration, or percutaneous administration. Therefore, the pharmaceutical composition comprising the compound according to the present invention as active ingredient may be formulated into suitable dosage forms according to the administration routes.

Specifically, oral preparations include tablets, capsules, powders, granules, and syrups, and parental preparations include injections, suppositories, tapes, and ointments.

These various preparations may be prepared by conventional methods, for example, with commonly used component, such as excipients, disintegrants, binders, lubricants, colorants, and diluents.

Excipients include, for example, lactose, glucose, corn starch, sorbit, and crystalline cellulose; disintegrants include, for example, starch, sodium alginate, gelatin powder, calcium carbonate, calcium citrate, and dextrin; binders include, for example, dimethylcellulose, polyvinyl alcohol, polyvinyl ether, methylcellulose, ethylcellulose, gum arabic, gelatin, hydroxypropylcellulose, polyvinyl pyrrolidone, carboxymethylcellulose sodium salt, and chremophore; lubricants include, for example, talc, magnesium stearate, polyethylene glycol, and hydrogenated vegetable oils.

In preparing injections, if necessary, for example, buffers, pH adjustors, stabilizers, tonicity agents, and preservatives may be added.

The dose of the compound according to the present invention in the pharmaceutical composition may vary depending upon the dosage form. In general, however, the dose is about 0.5 to 50% by weight, preferably about 1 to 20% by weight, based on the whole composition.

The dose may be appropriately determined depending upon, for example, the age, weight, sex, difference in diseases, and severity of condition of patients, and the active ingredient may be administered, for example, in an amount of 0.1 to 100 mg/kg, preferably 0.1 to 30 mg/kg. This dose can be administered at a time daily or divided doses of several times daily.

EXAMPLES

The present invention will be described in more detail with reference to the following examples, though it is not limited to these examples only.

Production Example 1 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline

Sodium hydride (60 wt %, 0.20 g) was added to dimethyl sulfoxide (15 ml), and the mixture was stirred at room temperature for 10 min. 4-Amino-3-nitrophenol (0.77 g) was added thereto, and the mixture was stirred at room temperature for 10 min. Next, 4-chloro-6,7-dimethoxyquinazoline (1.12 g) was added thereto, and the mixture was stirred at 100° C. for 3 hr. Water was added to the reaction solution, followed by extraction with chloroform. The chloroform layer was then washed with a 1 N aqueous sodium hydroxide solution and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and methanol was added to the residue to prepare a suspension. The precipitated crystal was collected by suction filtration to give the title compound (1.10 g, yield 64%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.07 (s, 3H), 4.08 (s, 3H), 6.10-6.15 (m, 2H), 6.92 (d, J=9.0 Hz, 1H), 7.34 (s, 1H), 7.35 (dd, J=9.0 Hz, J=2.7 Hz, 1H), 7.52 (s, 1H), 8.06 (d, J=2.9 Hz, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 343 (M⁺+1)

Production Example 2 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline

4-Chloro-6,7-dimethoxyquinazoline (10.23 g) and 2-fluoro-4-nitrophenol (14.37 g) were suspended in monochlorobenzene (100 ml), and the suspension was heated under reflux overnight. The solvent was removed by distillation under the reduced pressure, and the residue was washed with toluene, was filtered, and was dried. The crystal thus obtained was then suspended in an aqueous sodium hydroxide solution, and the suspension was filtered, followed by drying to give 4-(3-fluoro-4-nitrophenoxy)-6,7-dimethoxyquinoline (14.2 g, yield 90%). 4-(2-Fluoro-4-nitrophenoxy)-6,7-dimethoxy-quinoline (4.57 g) was dissolved in ethyl acetate/N,N-dimethylformamide/triethylamine (100 ml/100 ml/20 ml) to prepare a solution. Palladium hydroxide (1.2 g) was added to the solution, and the mixture was stirred in a hydrogen atmosphere at room temperature overnight. After filtration through Celite, the solvent was removed by distillation under the reduced pressure. A saturated aqueous sodium hydrogencarbonate solution was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure to quantitatively give 4.27 g of the title compound.

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.85 (m, 2H), 4.07 (s, 3H), 4.08 (s, 3H), 6.50-6.60 (m, 3H), 7.02-7.07 (m, 1H), 7.55-7.65 (m, 2H), 8.48 (d, J=5.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 315 (M⁺+1)

Production Example 3 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline

Sodium hydride (60 wt %, 0.72 g) was added to dimethyl sulfoxide (10 ml), and the mixture was stirred at 50° C. for 20 min. 4-Amino-3-chlorophenol hydrochloride (1.61 g) was added thereto, and the mixture was stirred at room temperature for 10 min. Next, 4-chloro-6,7-dimethoxyquinoline (1.00 g) was added thereto, and the mixture was stirred at 100° C. overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was then washed with a saturated aqueous sodium hydrogencarbonate solution and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. Methanol was added to the residue, and the precipitated crystal was collected by suction filtration to give the title compound (0.80 g, yield 60%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.06 (s, 3H), 4.07 (s, 3H), 6.36 (d, J=5.4 Hz, 1H), 6.65 (dd, J=8.5 Hz, J=2.9 Hz, 1H), 6.76 (d, J=8.8 Hz, 1H), 7.34 (d, J=8.5 Hz, 1H), 7.51 (s, 1H), 8.46 (d, J=6.0 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 332 (M⁺+1)

Production Example 4 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylaniline

4-Chloro-6,7-dimethoxyquinazoline (5.00 g) and 4-nitro-2-methylphenol (6.85 g) were suspended in monochlorobenzene (25 ml) to prepare a suspension which was then heated under reflux overnight. The solvent was removed by distillation under the reduced pressure. The residue was washed with ethyl acetate, was filtered, and was dried. Next, the resultant crystal was suspended in an aqueous sodium hydroxide solution to prepare a suspension. The suspension was then filtered, followed by drying to give 6.89 g of 4-(2-methyl-4-nitrophenoxy)-6,7-dimethoxyquinoline. 4-(2-Methyl-4-nitrophenoxy)-6,7-dimethoxyquinoline (1.36 g) was dissolved in ethyl acetate/N,N-dimethylformamide/triethylamine (25 ml/25 ml/5 ml). Palladium hydroxide (0.4 g) was added to the solution, and the mixture was stirred in a hydrogen atmosphere at room temperature overnight. After filtration through Celite, the solvent was removed by distillation under the reduced pressure. A saturated aqueous sodium hydrogencarbonate solution was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure to give the title compound (1.31 g, yield 91%).

Mass spectrometry value (ESI-MS, m/z): 311 (M⁺+1)

Production Example 5 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline

Sodium hydride (60 wt %, 3.2 g) was added to dimethyl sulfoxide (50 ml), and the mixture was stirred at 50° C. for 20 min. 4-Amino-3-methoxyphenol (5.6 g) was added thereto, and the mixture was stirred at room temperature for 10 min. Next, 4-chloro-6,7-dimethoxyquinazoline (7.0 g) was added thereto, and the mixture was stirred at 100° C. overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was then washed with a saturated aqueous sodium hydrogencarbonate solution and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. Methanol was added to the residue, and the precipitated crystal was collected by suction filtration to give the title compound (7.3 g, yield 72%).

Mass spectrometry value (ESI-MS, m/z): 328 (M⁺+1)

Example 1 4-Methylbenzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (129 mg) was added to toluene/triethylamine=10/1 (10 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (193 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methylbenzyl alcohol (79 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated, and the residue was purified on a column using chloroform/methanol to give the title compound (108 mg, yield 51%).

¹H-NMR (CDCl₃, 400 MHz): 8.61 (1H, s), 7.16-7.54 (10H, m), 6.70 (1H, s), 5.16 (2H, s), 4.05 (6H, s), 2.35 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 446 (M⁺+1)

Example 2 4-Methylbenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)-oxy]aniline (109 mg) was added to toluene/triethylamine=10/1 (10 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (146 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. subsequently, 4-methylbenzyl alcohol (61 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 28%).

¹H-NMR (CDCl₃, 400 MHz): 8.61 (1H, s), 8.29 (1H, d, J=9.0), 7.50 (1H, s), 7.15-7.35 (8H, m), 5.18 (2H, s), 4.05 (3H, s), 4.05 (3H, s), 2.36 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 3 1-(3-Chlorophenyl)ethyl N-{4-((6,7-dimethoxy-4-quinazolinyl)oxy)phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (72 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (109 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-chloro-α-methylbenzyl alcohol (46 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 70%).

¹H-NMR (CDCl₃, 400 MHz): 8.44-8.50 (1H, m), 8.14 (1H, s), 7.58-7.64 (3H, m), 7.26-7.42 (4H, m), 7.15-7.19 (2H, m), 6.86 (1H, s), 6.67 (1H, d, J=6.6), 5.88 (1H, q, J=6.6), 4.16

Example 4 1-(3-Chlorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (75 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (100 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-chloro-α-methylbenzyl alcohol (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 49%).

¹H-NMR (CDCl₃, 400 MHz): 8.41-8.47 (1H, m), 8.15 (1H, s), 7.71-7.76 (1H, m), 7.66 (1H, s), 7.25-7.45 (4H, m), 7.01 (1H, d, J=9.2 Hz), 6.50-6.55 (2H, m), 5.87 (1H, q, J=6.5 Hz), 4.17 (3H, s), 4.11 (3H, s), 2.27 (3H, s), 2.10 (3H, s), 1.62 (3H, d, J=6.5 Hz)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 5 1-(3-Chlorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (75 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (110 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-chloro-α-methylbenzyl alcohol (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (70 mg, yield 56%).

¹H-NMR (CDCl₃, 400 MHz): 8.37-8.44 (1H, m), 8.07 (1H, s), 7.82 (1H, bs), 7.57 (1H, s), 7.34 (1H, s), 7.20-7.26 (3H, m), 6.88 (1H, s), 6.49 (1H, d, J=6.6 Hz), 6.44 (1H, m), 5.80 (1H, q, J=6.6 Hz), 4.10 (3H, s), 4.03 (3H, s), 2.22 (3H, s), 2.04 (3H, s), 1.56 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 6 1-(3-Chlorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (72 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (100 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 15 min. Subsequently, 3-chloro-α-methylbenzyl alcohol (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (71 mg, yield 57%).

¹H-NMR (CDCl₃, 400 MHz): 8.76 (1H, s), 8.07 (1H, s), 7.50-7.60 (3H, m), 7.15-7.39 (5H, m), 6.83 (1H, s), 6.75-6.78 (1H, m), 5.84 (1H, q, J=6.8 Hz), 4.16 (3H, s), 4.09 (3H, s), 1.59 (3H, d, J=6.8 Hz)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 7 1-(3-Chlorophenyl)ethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (72 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (105 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-chloro-α-methylbenzyl alcohol (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (43 mg, yield 36%).

¹H-NMR (CDCl₃, 400 MHz): 8.77 (1H, s), 8.33 (1H, d, J=9.0 Hz), 8.06 (1H, s), 7.55 (1H, s), 7.39 (1H, s), 7.22-7.32 (6H, m), 5.85 (1H, q, J=6.7 Hz), 4.16 (3H, s), 4.09 (3H, s), 1.61 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 415 (M⁺+1)

Example 8 4-Fluorobenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (72 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (108 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluorobenzyl alcohol (40 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 58%).

¹H-NMR (CDCl₃, 400 MHz): 8.44-8.50 (1H, m), 8.14 (1H, s), 7.63 (1H, s), 7.56-7.66 (2H, m), 7.38-7.44 (2H, m), 7.16-7.20 (2H, m), 7.05-7.11 (2H, m), 6.85 (1H, s), 6.68 (1H, s), 5.20 (2H, s), 4.17 (3H, s), 4.10 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 429 (M⁺+1)

Example 9 4-Fluorobenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (78 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (110 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluorobenzyl alcohol (40 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 62%).

¹H-NMR (CDCl₃, 400 MHz): 8.42-8.47 (1H, m), 8.16 (1H, s), 7.66 (1H, s), 6.99-7.45 (6H, m), 6.50-6.56 (2H, m), 5.20 (2H, s), 4.17 (3H, s), 4.11 (3H, s), 2.25 (3H, s), 2.10 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 477 (M⁺+1)

Example 10 4-Fluorobenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (82 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (111 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluorobenzyl alcohol (40 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 68%).

¹H-NMR (CDCl₃, 400 MHz): 8.43-8.48 (1H, m), 8.15 (1H, m), 7.91 (1H, s), 7.64 (1H, s), 6.94-7.53 (6H, m), 6.57 (1H, d, J=6.6 Hz), 6.49 (1H, s), 5.20 (2H, s), 4.17 (3H, s), 4.11 (3H, s), 2.27 (3H, s), 2.13 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 477 (M⁺+1)

Example 11 4-Fluorobenzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (115 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluorobenzyl alcohol (45 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (43 mg, yield 33%).

¹H-NMR (CDCl₃, 400 MHz): 8.64 (1H, s), 7.56 (1H, s), 7.00-7.54 (9H, m), 6.72 (1H, s), 5.19 (2H, s), 4.09 (3H, s), 4.08 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 450 (M⁺+1)

Example 12 4-Fuorobenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (72 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (116 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluorobenzyl alcohol (45 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (38 mg, yield 34%).

¹H-NMR (CDCl₃, 400 MHz): 8.64 (1H, s), 8.30 (1H, d, J=9.3 Hz), 7.52 (1H, s), 7.40-7.45 (3H, m), 7.32-7.34 (1H, m), 7.18-7.22 (2H, m), 7.06-7.12 (2H, m), 5.21 (2H, s), 4.08 (3H, s), 4.07 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 485 (M⁺+1)

Example 13 1-(2-Chlorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (69 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (103 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 15 min. Subsequently, 2-chloro-α-methylbenzyl alcohol (55 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 64%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.48 (1H, m), 8.14 (1H, s), 7.15-7.64 (9H, m), 6.86 (1H, s), 6.67 (1H, d, J=6.6 Hz), 6.28 (1H, q, J=6.6 Hz), 4.16 (3H, s), 4.19 (3H, s), 1.63 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 14 1-(2-Chlorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (67 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (92 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 15 min. Subsequently, 2-chloro-α-methylbenzyl alcohol (48 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 79%).

¹H-NMR (CDCl₃, 400 MHz): 8.43 (1H, d, J=6.6 Hz), 8.14 (1H, s), 7.72-7.78 (1H, m), 7.66 (1H, s), 7.25-7.54 (4H, m), 7.00 (1H, d, J=8.6 Hz), 6.50-6.57 (2H, m), 6.27 (1H, q, J=6.6 Hz), 4.17 (3H, s), 4.11 (3H, s), 2.27 (3H, s), 2.09 (3H, s), 1.63 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 15 1-(2-Chlorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (62 mg) was added to toluene/triethylamine=10/1 (6 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (93 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 15 min. Subsequently, 2-chloro-α-methylbenzyl alcohol (49 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (52 mg, yield 48%).

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 16 1-(2-Chlorophenyl)ethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (61 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (91 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 15 min. Subsequently, 2-chloro-α-methylbenzyl alcohol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 69%).

¹H-NMR (CDCl₃, 400 MHz): 8.77 (1H, s), 8.36 (1H, d, J=8.8 Hz), 8.00-8.05 (1H, m), 7.16-7.57 (8H, m), 6.28 (1H, q, J=6.8 Hz), 4.17 (3H, s), 4.10 (3H, s), 1.63 (3H, d, J=6.8 Hz)

Mass spectrometry value (ESI-MS, m/z): 515 (M⁺+1)

Example 17 3-(2-Chlorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (78 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (117 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-chlorophenoxy)-1-propanol (67 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 58%).

¹H-NMR (CDCl₃, 400 MHz): 8.43 (1H, d, J=5.4 Hz), 7.61 (1H, s), 7.48 (1H, s), 7.35-7.40 (1H, m), 7.18-7.25 (2H, m), 6.87-7.05 (3H, m), 6.43 (1H, bs), 6.27 (1H, d, J=4.9 Hz), 4.46 (2H, t, J=6.2 Hz), 4.05-4.22 (2H, m), 4.07 (3H, s), 4.06 (3H, s), 2.24 (3H, s), 2.11 (3H, s), 2.10-2.22 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 538 (M⁺+1)

Example 18 3-(2-Chlorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (71 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (97 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-chlorophenoxy)-1-propanol (72 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 44%).

¹H-NMR (CDCl₃, 400 MHz): 8.44 (1H, d, J=5.4 Hz), 7.50-7.80 (2H, m), 7.19-7.40 (3H, m), 6.88-6.98 (3H, m), 6.35-6.48 (2H, m), 4.65 (2H, t, J=6.2 Hz), 4.18 (2H, t, J=6.0 Hz), 4.07 (3H, s), 4.07 (3H, s), 2.10-2.30 (8H, m)

Mass spectrometry value (ESI-MS, m/z): 538 (M⁺+1)

Example 19 3-(2-Chlorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (77 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (115 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-chlorophenoxy)-1-propanol (72 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 44%).

¹H-NMR (CDCl₃, 400 MHz): 8.62-8.64 (1H, m), 7.55-7.57 (1H, m), 7.48-7.53 (2H, m), 7.35-7.40 (2H, m), 7.19-7.28 (3H, m), 6.87-6.97 (2H, m), 6.77 (1H, bs), 4.43-4.48 (2H, m), 4.14-4.20 (2H, m), 4.08 (3H, s), 4.07 (3H, s), 2.15-2.28 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 511 (M⁺+1)

Example 20 3-(2-Chlorophenoxy)propyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (70 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (94 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-chlorophenoxy)-1-propanol (59 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 50%).

¹H-NMR (CDCl₃, 400 MHz): 8.63 (1H, s), 8.25-8.35 (1H, d), 7.52 (1H, s), 7.14-7.41 (6H, m), 6.88-6.98 (2H, m), 4.48 (2H, t, J=6.2 Hz), 4.18 (2H, t, J=6.2 Hz), 4.08 (3H, s), 4.07 (3H, s), 2.10-2.50 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 545 (M⁺+1)

Example 21 4-(Trifluoromethyl)benzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (75 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (112 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-trifluoromethylbenzyl alcohol (67 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 57%).

¹H-NMR (CDCl₃, 400 MHz): 8.43-8.48 (1H, m), 8.14 (1H, s), 7.47-7.70 (7H, m), 7.15-7.22 (3H, m), 6.68 (1H, d, J=6.6 Hz), 5.29 (2H, s), 4.16 (3H, s), 4.10 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 499 (M⁺+1)

Example 22 4-(Trifluoromethyl)benzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (77 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (105 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-trifluoromethylbenzyl alcohol (63 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 60%).

¹H-NMR (CDCl₃, 400 MHz): 8.44 (1H, d, J=6.4 Hz), 8.00-8.15 (1H, m), 7.53-7.69 (6H, m), 7.03 (1H, d, J=9.0 Hz), 6.54-6.65 (1H, m), 6.47-6.53 (1H, m), 5.29 (3H, s), 4.15 (3H, s), 4.11 (3H, s), 2.27 (3H, s), 2.11 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 528 (M⁺+1)

Example 23 4-(Trifluoromethyl)benzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (77 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (105 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-trifluoromethylbenzyl alcohol (63 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 48%).

¹H-NMR (CDCl₃, 400 MHz): 8.43-8.48 (1H, m), 8.16 (1H, s), 7.50-7.95 (6H, m), 6.97 (1H, s), 6.55-6.60 (2H, m), 5.29 (2H, m), 4.17 (3H, s), 4.11 (3H, s), 2.29 (3H, s), 2.14 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 528 (M⁺+1)

Example 24 4-(Trifluoromethyl)benzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (70 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (105 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-trifluoromethylbenzyl alcohol (63 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 48%).

¹H-NMR (CDCl₃, 400 MHz): 8.70 (1H, s), 7.48-7.78 (8H, m), 7.20-7.24 (2H, m), 6.94 (1H, bs), 5.28 (2H, s), 4.13 (3H, s), 4.10 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 500 (M⁺+1)

Example 25 4-(Trifluoromethyl)benzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (74 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (99 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-trifluoromethylbenzyl alcohol (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (52 mg, yield 41%).

¹H-NMR (CDCl₃, 400 MHz): 8.62-8.65 (1H, m), 8.25-8.34 (1H, m), 7.16-7.71 (9H, m), 5.27-5.31 (2H, m), 4.05-4.08 (6H, m)

Mass spectrometry value (ESI-MS, m/z): 535 (M⁺+1)

Example 26 3-(2-chlorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (61 mg) was added to toluene/triethylamine=10/1 (6 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (91 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-chlorophenoxy)-1-propanol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 69%).

¹H-NMR (CDCl₃, 400 MHz): 8.43-8.50 (1H, m), 8.15 (1H, s), 7.64 (1H, s), 7.56-7.65 (2H, m), 6.89-7.40 (6H, m), 6.81 (1H, s), 6.68 (1H, d, J=6.4 Hz), 4.48 (2H, t, J=6.2 Hz), 4.15-4.22 (2H, m), 4.17 (3H, s), 4.10 (3H, s), 2.20-2.30 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 510 (M⁺+1)

Example 27 3-(4-Chlorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (79 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-chlorophenoxy)-1-propanol (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 55%).

¹H-NMR (CDCl₃, 400 MHz): 8.44-8.50 (1H, m), 8.15 (1H, s), 7.63 (1H, s), 7.52-7.64 (4H, m), 6.77-6.87 (3H, m), 6.68 (1H, d, J=6.3 Hz), 4.41 (2H, t, J=6.3 Hz), 4.17 (3H, s), 4.10 (3H, s), 4.05-4.10 (2H, m), 2.15-2.22 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 510 (M⁺+1)

Example 28 3-(4-Chlorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (115 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-chlorophenoxy)-1-propanol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (84 mg, yield 60%).

¹H-NMR (CDCl₃, 400 MHz): 8.41-8.48 (1H, m), 8.16 (1H, s), 7.65-7.75 (1H, m), 6.82-7.27 (7H, m), 6.43-6.58 (1H, m), 4.41 (2H, d, J=6.3 Hz), 4.17 (3H, s), 4.11 (3H, s), 4.05-4.15 (2H, m), 2.26 (3H, s), 2.10 (3H, s), 2.00-2.08 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 538 (M⁺+1)

Example 29 3-(4-Chlorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (78 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (115 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-chlorophenoxy)-1-propanol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (71 mg, yield 51%).

¹H-NMR (CDCl₃, 400 MHz): 8.43-8.48 (1H, m), 8.15 (1H, s), 7.88 (1H, bs), 7.64 (1H, s), 6.82-7.26 (6H, m), 6.57 (1H, d, J=6.6 Hz), 6.43 (1H, bs), 4.12 (2H, t, J=6.6 Hz), 4.17 (3H, s), 4.11 (3H, s), 4.05-4.11 (2H, m), 2.28 (3H, s), 2.15-2.23 (2H, m), 2.12 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 538 (M⁺+1)

Example 30 3-(4-Chlorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (78 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-chlorophenoxy)-1-propanol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 37%).

¹H-NMR (CDCl₃, 400 MHz): 8.79 (1H, s), 8.14 (1H, s), 7.61 (1H, s), 7.53-7.58 (2H, m), 7.16-7.26 (4H, m), 6.76-6.86 (3H, m), 4.40 (2H, t, J=6.2 Hz), 4.19 (3H, s), 4.12 (3H, s), 4.02-4.10 (2H, m), 2.15-2.21 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 511 (M⁺+1)

Example 31 3-(4-Chlorophenoxy)propyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (75 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (121 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-chlorophenoxy)-1-propanol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (58 mg, yield 44%).

¹H-NMR (CDCl₃, 400 MHz): 8.70 (1H, s), 8.25-8.35 (1H, m), 7.65-7.70 (1H, m), 7.54 (1H, s), 7.15-7.35 (4H, m), 6.82-6.87 (3H, m), 4.42 (2H, t, J=6.4 Hz), 4.12 (3H, s), 4.09 (3H, s), 4.05-4.13 (2H, m), 2.17-2.25 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 545 (M⁺+1)

Example 32 1-(4-Methoxyphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (73 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (110 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methoxy-α-methylbenzyl alcohol (56 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (74 mg, yield 59%).

¹H-NMR (CDCl₃, 400 MHz): 8.44-8.48 (1H, m), 8.14 (1H, s), 7.63 (1H, s), 7.55-7.62 (2H, m), 7.33-7.38 (2H, m), 7.14-7.18 (2H, m), 6.88-6.94 (2H, m), 6.79 (1H, s), 6.67 (1H, d, J=6.4 Hz), 5.86-5.93 (1H, m), 4.16 (3H, s), 4.10 (3H, s), 3.82 (3H, s), 1.63 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 476 (M⁺+1)

Example 33 1-(4-Methoxyphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (68 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (94 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methoxy-α-methylbenzyl alcohol (48 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (75 mg, yield 66%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.45 (1H, m), 8.15 (1H, s), 7.73-7.78 (1H, m), 7.66 (1H, s), 7.33-7.38 (2H, m), 6.98-7.02 (1H, m), 6.89-6.94 (2H, m), 6.53 (1H, d, J=6.6 Hz), 6.46 (1H, bs), 5.85-5.92 (1H, m), 4.20 (3H, s), 4.11 (3H, s), 3.82 (3H, s), 2.24 (3H, s), 2.09 (3H, s), 1.63 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 504 (M⁺+1)

Example 34 1-(4-Methoxyphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (110 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methoxy-α-methylbenzyl alcohol (56 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 60%).

¹H-NMR (CDCl₃, 400 MHz): 8.41-8.47 (1H, m), 8.15 (1H, s), 7.92 (1H, s), 7.64 (1H, s), 6.80-7.40 (5H, m), 6.55 (1H, d, J=6.6 Hz), 6.44 (1H, s), 5.85-5.92 (1H, m), 4.17 (3H, s), 4.11 (3H, s), 3.82 (3H, s), 2.26 (3H, s), 2.11 (3H, s), 1.64 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 504 (M⁺+1)

Example 35 1-(4-Methoxyphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (68 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (102 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methoxy-α-methylbenzyl alcohol (52 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 52%).

¹H-NMR (CDCl₃, 400 MHz): 8.72 (1H, s), 7.85 (1H, s like), 7.58 (1H, s), 7.48-7.55 (2H, m), 7.32-7.37 (2H, m), 7.15-7.20 (2H, m), 6.87-6.93 (2H, m), 6.72 (1H, s), 5.85-5.92 (1H, m), 4.14 (3H, s), 4.10 (3H, s), 3.81 (3H, s), 1.61 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 477 (M⁺+1)

Example 36 1-(4-Methoxyphenyl)ethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (66 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (88 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methoxy-α-methylbenzyl alcohol (45 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (58 mg, yield 53%).

¹H-NMR (CDCl₃, 400 MHz): 8.76 (1H, s like), 8.32-8.40 (1H, m), 6.88-8.00 (9H, m), 5.87-5.93 (1H, m), 4.16 (3H, s), 4.10 (3H, s), 3.82 (3H, s), 1.63 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 511 (M⁺+1)

Example 37 3-[(4-Methylphenyl)sulfanyl)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (121 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[(4-methylphenyl)sulfanyl]-1-propanol (74 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (98 mg, yield 67%).

¹H-NMR (CDCl₃, 400 MHz): 8.44-8.50 (H, m), 8.15 (1H, s), 7.64 (1H, s), 7.55-7.64 (2H, m), 7.10-7.31 (6H, m), 6.77 (1H, s), 6.69 (1H, d, J=6.6 Hz), 4.32 (2H, t, J=6.2 Hz), 4.17 (3H, s), 4.10 (3H, s), 2.97-3.03 (2H, m), 2.33 (3H, s), 1.95-2.05 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 38 3-[(4-Methylphenyl)sulfanyl)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (85 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (122 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[(4-methylphenyl)sulfanyl]-1-propanol (72 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (93 mg, yield 62%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.48 (1H, m), 8.16 (1H, s), 7.65-7.77 (2H, m), 7.00-7.31 (5H, m), 6.55 (1H, d, J=6.4 Hz), 6.40-6.50 (1H, m), 4.29-4.40 (1H, m), 4.17 (3H, s), 4.11 (3H, s), 3.74-3.80 (1H, m), 2.95-3.05 (2H, m), 2.26-2.34 (6H, m), 2.10 (3H, s), 1.84-2.04 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 39 3-[(4-Methylphenyl)sulfanyl)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (85 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[(4-methylphenyl)sulfanyl]-1-propanol (72 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (82 mg, yield 56%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.49 (1H, m), 8.16 (1H, s), 7.85-7.92 (1H, m), 7.64 (1H, s), 7.08-7.32 (4H, m), 6.95 (1H, s), 6.57 (1H, d, J=6.6 Hz), 6.40 (1H, s), 4.30-4.40 (2H, m), 4.17 (3H, s), 4.11 (3H, s), 2.95-3.15 (2H, m), 2.27-2.34 (6H, m), 2.13 (3H, s), 1.98-2.06 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 524 (M⁺+1)

Example 40 3-[(4-Methylphenyl)sulfanyl)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[(4-methylphenyl)sulfanyl]-1-propanol (74 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (82 mg, yield 56%).

¹H-NMR (CDCl₃, 400 MHz): 8.66 (1H, s), 7.57 (1H, s), 7.48-7.55 (2H, m), 7.10-7.31 (7H, m), 6.65 (1H, bs), 4.27-4.38 (2H, m), 4.10 (3H, s), 4.09 (3H, s), 2.95-3.15 (2H, m), 2.32 (3H, s), 1.95-2.05 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 507 (M⁺+1)

Example 41 3-[(4-Methylphenyl)sulfanyl)propyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (125 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[(4-methylphenyl)sulfanyl]-1-propanol (66 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 49%).

¹H-NMR (CDCl₃, 400 MHz): 8.76 (1H, s), 8.31-8.38 (1H, m), 7.91 (1H, bs), 7.56 (2H, s), 7.10-7.34 (6H, m), 4.30-4.43 (2H, m), 4.16 (3H, s), 4.11 (3H, s), 3.00 (2H, t, J=7.0 Hz), 2.32 (3H, s), 1.97-2.06 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 541 (M⁺+1)

Example 42 3-(4-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-methoxyphenoxy)-1-propanol (73 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (118 mg, yield 80%).

¹H-NMR (CDCl₃, 400 MHz): 8.44-8.48 (1H, m), 8.14 (1H, s), 7.64 (1H, s), 7.57-7.64 (2H, m), 7.15-7.20 (2H, m), 6.83-6.87 (5H, m), 6.65-6.72 (1H, m), 4.17 (3H, s), 4.10 (3H, s), 4.42 (2H, t, J=6.2 Hz), 4.06 (2H, t, J=6.2 Hz), 3.77 (3H, s), 2.17 (2H, t, J=6.2 Hz)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 43 3-(4-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (88 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (122 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-methoxyphenoxy)-1-propanol (74 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (128 mg, yield 83%).

¹H-NMR (CDCl₃, 400 MHz): 8.42-8.46 (1H, m), 8.16 (1H, s), 7.66-7.75 (1H, m), 7.02 (1H, d, J=8.8 Hz), 6.80-6.87 (5H, m), 6.55 (1H, d, J=6.6 Hz), 6.46 (1H, bs), 4.41 (2H, t, J=6.4 Hz), 4.17 (3H, s), 4.11 (3H, s), 4.04-4.10 (2H, m), 3.77 (3H, s), 2.26 (3H, s), 2.10 (3H, s), 2.14-2.21 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 44 3-(4-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (98 mg) was added to toluene/triethylamine=10/1 (10 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (136 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-methoxyphenoxy)-1-propanol (83 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (130 mg, yield 76%).

¹H-NMR (CDCl₃, 400 MHz): 8.43-8.47 (1H, m), 8.15 (1H, s), 7.89 (1H, bs), 7.64 (1H, s), 6.80-6.97 (5H, m), 6.57 (1H, d, J=6.6 Hz), 6.44 (1H, s), 4.42 (2H, t, J=6.3 Hz), 4.17 (3H, s), 4.11 (3H, s), 4.06 (2H, t, J=6.3 Hz), 3.77 (3H, s), 2.28 (3H, s), 2.14-2.24 (2H, m), 2.12 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 45 3-(4-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (82 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (122 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-methoxyphenoxy)-1-propanol (75 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (92 mg, yield 62%).

¹H-NMR (CDCl₃, 400 MHz): 8.66 (1H, s), 7.57 (1H, s), 7.40-7.54 (3H, m), 7.18-7.24 (2H, m), 6.65-6.85 (5H, m), 4.40 (2H, t, J=63 Hz), 4.09 (3H, s), 4.08 (3H, s), 4.05 (2H, t, J=6.1 Hz), 3.77 (3H, s), 2.10-2.20 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 507 (M⁺+1)

Example 46 3-(4-Methoxyphenoxy)propyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (87 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (117 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-methoxyphenoxy)-1-propanol (72 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 45%).

¹H-NMR (CDCl₃, 400 MHz): 8.68 (1H, s), 8.30 (1H, d, J=8.5 Hz), 7.53-7.60 (2H, m), 6.80-7.34 (7H, m), 4.42 (2H, t, J=6.4 Hz), 4.11 (3H, s), 4.08 (3H, s), 4.06 (2H, t, J=6.2 Hz), 3.77 (3H, s), 2.15-2.22 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 540 (M⁺+1)

Example 47 3-(3-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (75 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (112 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(3-methoxyphenoxy)-1-propanol (69 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 69%).

¹H-NMR (CDCl₃, 400 MHz): 8.45-8.51 (1H, m), 8.14 (1H, s), 7.63 (1H, s), 7.54-7.64 (2H, m), 7.15-7.23 (3H, m), 6.82 (1H, s), 6.69 (1H, d, J=6.6 Hz), 6.45-6.55 (3H, m), 4.42 (2H, t, J=6.2 Hz), 4.17 (3H, s), 4.10 (3H, s), 4.09 (2H, t, J=6.1 Hz), 3.79 (3H, s), 2.15-2.22 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 48 3-(3-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (85 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (116 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(3-methoxyphenoxy)-1-propanol (72 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (91 mg, yield 72%).

¹H-NMR (CDCl₃, 400 MHz): 8.43 (1H, d, J=5.4 Hz), 7.50-7.63 (2H, m), 6.28-7.24 (8H, m), 4.40 (2H, t, J=6.3 Hz), 4.07 (6H, s), 4.05-4.10 (2H, m), 3.79 (3H, s), 2.24 (3H, s), 2.15-2.23 (2H, m), 2.11 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 49 3-(3-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (77 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (105 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(3-methoxyphenoxy)-1-propanol (65 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (91 mg, yield 72%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.48 (1H, m), 8.15 (1H, s), 7.89 (1H, s), 8.63-8.68 (1H, m), 6.93-7.25 (2H, m), 6.40-6.59 (5H, m), 4.38-4.45 (2H, m), 4.17 (3H, s), 4.11 (3H, s), 4.05-4.14 (2H, m), 3.79 (3H, s), 2.15-2.25 (2H, m), 2.28 (3H, s), 2.12 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 50 3-(3-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (95 mg) was added to toluene/triethylamine=10/1 (10 ml), and the mixture was then added to the solution, and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (142 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(3-methoxyphenoxy)-1-propanol (87 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (105 mg, yield 65%).

¹H-NMR (CDCl₃, 400 MHz): 8.69 (1H, s), 7.45-7.97 (3H, m), 7.13-7.21 (3H, m), 6.40-6.80 (5H, m), 4.38 (2H, t, J=6.4 Hz), 4.10 (3H, s), 4.07 (3H, s), 3.98-4.08 (2H, m), 3.77 (3H, s), 2.08-2.20 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 507 (M⁺+1)

Example 51 3-(3-Methoxyphenoxy)propyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (107 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(3-methoxyphenoxy)-1-propanol (67 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (67 mg, yield 52%).

¹H-NMR (CDCl₃, 400 MHz): 8.70 (1H, s), 8.31 (1H, d, J=9.0 Hz), 7.54 (1H, s), 7.33 (1H, d, J=2.7 Hz), 7.15-7.23 (3H, m), 6.47-6.55 (4H, m), 4.43 (2H, t, J=6.2 Hz), 4.12 (3H, s), 4.09 (3H, s), 4.08-4.13 (2H, m), 3.79 (3H, s), 2.15-2.25 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 541 (M⁺+1)

Example 52 1-(3-Methoxyphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (83 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (124 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-methoxy-α-methylbenzyl alcohol (64 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 66%).

¹H-NMR (CDCl₃, 400 MHz): 8.46 (1H, dd, J=6.5 Hz), 8.14 (1H, s), 7.58-7.64 (2H, m), 7.38-7.42 (1H, m), 7.29-7.32 (1H, m), 7.14-7.18 (2H, m), 6.96-7.02 (1H, m), 6.91 (1H, d, J=8.3 Hz), 6.86 (1H, s), 6.68 (1H, d, J=6.6 Hz), 6.29 (1H, q, J=6.5 Hz), 4.16 (3H, s), 4.10 (3H, s), 3.88 (3H, s), 1.58 (3H, d, J=6.5 Hz)

Mass spectrometry value (ESI-MS, m/z): 476 (M⁺+1)

Example 53 1-(3-Methoxyphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (123 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-methoxy-α-methylbenzyl alcohol (64 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (97 mg, yield 70%).

¹H-NMR (CDCl₃, 400 MHz): 8.41-8.46 (1H, m), 8.15 (1H, s), 7.77 (1H, d, J=8.6 Hz), 7.66 (1H, s), 7.40 (1H, d, J=7.8 Hz), 7.30 (1H, d, J=7.3 Hz), 6.96-7.20 (2H, m), 6.91 (1H, d, J=8.3 Hz), 6.50-6.55 (2H, m), 6.29 (1H, q, J=6.5 Hz), 4.17 (3H, s), 4.11 (3H, s), 3.87 (3H, s), 2.27 (3H, s), 2.09 (3H, s), 1.59 (3H, d, J=6.5 Hz)

Mass spectrometry value (ESI-MS, m/z): 504 (M⁺+1)

Example 54 1-(3-Methoxyphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (123 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-methoxy-α-methylbenzyl alcohol (64 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (78 mg, yield 56%).

¹H-NMR (CDCl₃, 400 MHz): 8.41-8.48 (1H, m), 8.12 (1H, s), 7.92 (1H, s), 7.62 (1H, s), 7.26-7.42 (2H, m), 6.85-7.00 (3H, m), 6.45-6.58 (2H, m), 6.27 (1H, q, J=6.5 Hz), 4.14 (3H, s), 4.08 (3H, s), 3.86 (3H, s), 2.27 (3H, s), 2.08 (3H, s), 1.57 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 504 (M⁺+1)

Example 55 1-(3-Methoxyphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (83 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (124 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-methoxy-α-methylbenzyl alcohol (64 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (76 mg, yield 58%).

¹H-NMR (CDCl₃, 400 MHz): 8.75 (1H, s), 8.00 (1H, bs), 7.16-7.62 (7H, m), 6.88-7.02 (2H, m), 6.79 (1H, bs), 6.28 (1H, q, J=6.4 Hz), 4.16 (3H, s), 4.11 (3H, s), 3.87 (3H, s), 1.58 (3H, d, J=6.4 Hz)

Mass spectrometry value (ESI-MS, m/z): 477 (M⁺+1)

Example 56 1-(3-Methoxyphenyl)ethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (82 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (110 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-methoxy-α-methylbenzyl alcohol (56 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (69 mg, yield 55%).

¹H-NMR (CDCl₃, 400 MHz): 8.80 (1H, s), 8.40 (1H, d, J=9.0 Hz), 8.14 (1H, s), 7.14-7.60 (5H, m), 6.97-7.03 (1H, m), 6.91 (1H, d, J=8.3 Hz), 6.30 (1H, q, J=6.5 Hz), 4.19 (3H, s), 4.12 (3H, s), 3.88 (3H, s), 1.60 (3H, d, J=6.5 Hz)

Mass spectrometry value (ESI-MS, m/z): 511 (M⁺+1)

Example 57 4-(Tert-butyl)benzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (137 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methoxy-tert-butylbenzyl alcohol (75 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (109 mg, yield 69%).

¹H-NMR (CDCl₃, 400 MHz): 8.46 (1H, dd, J=6.7 Hz), 8.15 (1H, s), 7.64 (1H, s), 7.59 (2H, d, J=9.0 Hz), 7.43 (2H, d, J=9.0 Hz), 7.36 (2H, d, J=8.3 Hz), 7.18 (2H, d, J=9.0 Hz), 6.82 (1H, s), 6.68 (1H, d, J=6.7 Hz), 5.21 (2H, s), 4.17 (3H, s), 4.19 (3H, s), 1.34 (9H, s)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 58 4-(Tert-butyl)benzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (83 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (115 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methoxy-tert-butylbenzyl alcohol (63 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (101 mg, yield 72%).

¹H-NMR (CDCl₃, 400 MHz): 8.42-8.47 (1H, m), 8.16 (1H, s), 7.75-7.85 (1H, m), 7.67 (1H, s), 7.44 (2H, d, J=8.6 Hz), 7.38 (2H, d, J=8.3 Hz), 7.03 (1H, d, J=9.0 Hz), 6.55 (1H, d, J=6.6 Hz), 6.52 (1H, bs), 5.21 (2H, s), 4.17 (3H, s), 4.11 (3H, s), 2.25 (3H, s), 2.09 (3H, s), 1.34 (9H, s)

Mass spectrometry value (ESI-MS, m/z): 516 (M⁺+1)

Example 59 4-(Tert-butyl)benzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (111 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methoxy-tert-butylbenzyl alcohol (61 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (93 mg, yield 68%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.47 (1H, m), 8.15 (1H, s), 7.95 (1H, bs), 7.64 (1H, s), 7.36-7.46 (4H, m), 6.95 (1H, s), 6.57 (1H, d, J=6.6 Hz), 6.50 (1H, s), 5.21 (2H, s), 4.17 (3H, s), 4.11 (3H, s), 2.26 (3H, s), 2.13 (3H, s), 1.34 (9H, s)

Mass spectrometry value (ESI-MS, m/z): 516 (M⁺+1)

Example 60 4-(Tert-butyl)benzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (95 mg) was added to toluene/triethylamine=10/1 (10 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (144 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methoxy-tert-butylbenzyl alcohol (79 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (71 mg, yield 42%).

¹H-NMR (CDCl₃, 400 MHz): 8.77 (1H, s), 8.07 (1H, bs), 7.61 (1H, s), 7.51-7.58 (2H, m), 7.42 (2H, d, J=8.6 Hz), 7.36 (2H, d, J=8.3 Hz), 7.19 (2H, d, J=9.0 Hz), 6.79 (1H, s), 5.20 (2H, s), 4.18 (3H, s), 4.12 (3H, s), 1.33 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 489 (M⁺+1)

Example 61 4-(Tert-butyl)benzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (122 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methoxy-tert-butylbenzyl alcohol (67 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (55 mg, yield 36%).

¹H-NMR (CDCl₃, 400 MHz): 8.80 (1H, s), 8.41 (1H, d, J=9.2 Hz), 8.13 (1H, s), 7.58 (1H, s), 7.36-7.46 (4H, m), 7.24-7.34 (2H, m), 7.17-7.22 (1H, m), 5.22 (2H, s), 4.19 (3H, s), 4.12 (3H, s), 1.34 (9H, s)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 62 3,4-Dimethoxybenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (65 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (100 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3,4-dimethoxybenzyl alcohol (55 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (70 mg, yield 60%).

¹H-NMR (CDCl₃, 400 MHz): 8.49 (1H, s), 8.14 (1H, s), 7.58-7.64 (3H, m), 7.17-7.22 (2H, m), 6.86-7.04 (4H, m), 6.69 (1H, m), 5.17 (2H, s), 4.17 (3H, s), 4.10 (3H, s), 3.92 (3H, s), 3.90 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 63 3,4-Dimethoxybenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (65 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (107 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3,4-dimethoxybenzyl alcohol (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (73 mg, yield 55%).

¹H-NMR (CDCl₃, 400 MHz): 8.46 (1H, dd, J=6.6 Hz), 8.15 (1H, s), 7.75-7.80 (1H, m), 7.66 (1H, s), 6.83-7.05 (4H, m), 6.55 (1H, d, J=6.4 Hz), 6.51 (1H, s), 5.17 (2H, s), 4.17 (3H, s), 4.12 (3H, s), 3.92 (3H, s), 3.91 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 520 (M⁺+1)

Example 64 3,4-Dimethoxybenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (89 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (124 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3,4-dimethoxybenzyl alcohol (72 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (102 mg, yield 67%).

¹H-NMR (CDCl₃, 400 MHz): 8.44-8.50 (1H, m), 8.12 (1H, s), 7.91 (1H, s), 7.62 (1H, s), 6.80-7.03 (4H, m), 6.55 (1H, d, J=6.3 Hz), 6.48 (1H, s), 5.15 (2H, s), 4.15 (3H, s), 4.08 (3H, s), 3.90 (3H, s), 3.88 (3H, s), 2.24 (3H, s), 2.11 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 519 (M⁺+1)

Example 65 3,4-Dimethoxybenzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (83 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (147 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3,4-dimethoxybenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (70 mg, yield 48%).

¹H-NMR (CDCl₃, 400 MHz): 8.79 (1H, s), 8.14 (1H, s), 7.54-7.64 (3H, m), 7.18-7.24 (2H, m), 6.79-7.01 (4H, m), 5.16 (2H, s), 4.19 (3H, s), 4.12 (3H, s), 3.92 (3H, s), 3.90 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 66 3,4-Dimethoxybenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (76 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (105 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3,4-dimethoxybenzyl alcohol (58 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (53 mg, yield 42%).

¹H-NMR (CDCl₃, 400 MHz): 8.68 (1H, s), 8.33 (1H, d, J=8.8 Hz), 7.50-7.60 (2H, m), 6.83-7.35 (6H, m), 5.18 (2H, s), 4.11 (3H, s), 4.08 (3H, s), 3.93 (3H, s), 3.90 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 527 (M⁺+1)

Example 67 2,5-Dimethoxybenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (75 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3,5-dimethoxybenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (90 mg, yield 68%).

¹H-NMR (CDCl₃, 400 MHz): 8.47 (1H, d like, J=6.6 Hz), 8.14 (1H, s), 6.67-7.66 (10H, m), 5.27 (2H, s), 4.17 (3H, s), 4.10 (3H, s), 3.84 (3H, s), 3.79 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 491 (M⁺+1)

Example 68 2,5-Dimethoxybenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (85 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3,5-dimethoxybenzyl alcohol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (92 mg, yield 60%).

¹H-NMR (CDCl₃, 400 MHz): 8.44 (1H, d, J=6.4 Hz), 8.05 (1H, s), 7.74-7.80 (1H, m), 7.66 (1H, s), 6.78-7.40 (4H, m), 6.50-6.58 (2H, m), 5.27 (2H, s), 4.16 (3H, s), 4.11 (3H, s), 3.85 (3H, s), 3.79 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 520 (M⁺+1)

Example 69 2,5-Dimethoxybenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (125 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3,5-dimethoxybenzyl alcohol (73 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (92 mg, yield 60%).

¹H-NMR (CDCl₃, 400 MHz): 8.46 (1H, d like, J=6.6 Hz), 8.15 (1H, s), 7.95 (1H, s), 7.65 (1H, s), 6.85-7.02 (4H, m), 6.58 (1H, d, J=6.6 Hz), 6.53 (2H, s), 5.28 (2H, s), 4.17 (3H, s), 4.11 (3H, s), 3.85 (3H, s), 3.80 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 519 (M⁺+1)

Example 70 2,5-Dimethoxybenzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (72 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3,5-dimethoxybenzyl alcohol (65 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (66 mg, yield 52%).

¹H-NMR (CDCl₃, 400 MHz): 8.80 (1H, s), 8.14 (1H, s), 7.55-7.63 (3H, m), 7.16-7.22 (2H, m), 6.83-7.00 (3H, m), 5.26 (2H, s), 4.19 (3H, s), 4.12 (3H, s), 3.83 (3H, s), 3.79 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 71 2,5-Dimethoxybenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (76 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (105 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3,5-dimethoxybenzyl alcohol (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (59 mg, yield 46%).

¹H-NMR (CDCl₃, 400 MHz): 8.75 (1H, s), 8.39 (1H, d, J=9.3 Hz), 6.73-7.85 (8H, m), 5.28 (2H, s), 4.15 (3H, s), 4.10 (3H, s), 3.84 (3H, s), 3.80 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 527 (M⁺+1)

Example 72 3-{[4-(Tert-butyl)phenyl]sulfanyl}-propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (72 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[4-(tert-butyl)phenyl]sulfanyl-1-propanol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (81 mg, yield 57%).

¹H-NMR (CDCl₃, 400 MHz): 8.45-8.50 (1H, m), 8.14 (1H, s), 7.64 (1H, s), 7.58-7.66 (2H, m), 7.16-7.33 (6H, m), 6.80 (1H, s), 6.69 (1H, d, J=6.6 Hz), 4.33 (2H, t, J=6.2 Hz), 4.17 (3H, s), 4.10 (3H, s), 3.01 (2H, t, J=7.2 Hz), 1.99-2.07 (2H, m), 1.31 (9H, s)

Mass spectrometry value (ESI-MS, m/z): 548 (M⁺+1)

Example 73 3-{[4-(Tert-butyl)phenyl]sulfanyl}-propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (78 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (121 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[4-(tert-butyl)phenyl]sulfanyl-1-propanol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (109 mg, yield 74%).

¹H-NMR (CDCl₃, 400 MHz): 8.44 (1H, d, J=5.4 Hz), 7.48-7.64 (3H, m), 7.27-7.35 (4H, m), 6.97-7.03 (1H, m), 6.38 (1H, bs), 6.28 (1H, d, J=5.4 Hz), 4.31 (2H, t, J=6.2 Hz), 4.07 (3H, s), 2.98-3.13 (2H, m), 2.25 (3H, s), 2.12 (3H, s), 1.98-2.06 (2H, m), 1.30 (9H, s)

Mass spectrometry value (ESI-MS, m/z): 576 (M⁺+1)

Example 74 3-{[4-(Tert-butyl)phenyl]sulfanyl}-propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (82 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (122 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[4-(tert-butyl)phenyl]sulfanyl-1-propanol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (113 mg, yield 73%).

¹H-NMR (CDCl₃, 400 MHz): 8.45-8.50 (1H, m), 8.15 (1H, s), 7.89 (1H, s), 7.65 (1H, s), 7.32 (4H, s), 6.95 (1H, s), 6.58 (1H, d, J=6.4 Hz), 6.44 (1H, s), 4.33 (2H, t, J=6.4 Hz), 4.17 (3H, s), 4.11 (3H, s), 3.02 (2H, t, J=7.1 Hz), 2.29 (3H, s), 2.13 (3H, s), 2.00-2.08 (2H, m), 1.31 (9H, s)

Mass spectrometry value (ESI-MS, m/z): 576 (M⁺+1)

Example 75 3-{[4-(Tert-butyl)phenyl]sulfanyl}-propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[4-(tert-butyl)phenyl]sulfanyl-1-propanol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (100 mg, yield 64%).

¹H-NMR (CDCl₃, 400 MHz): 8.73 (1H, s like), 8.52-8.60 (1H, m), 7.70-7.90 (2H, m), 6.80-7.65 (8H, m), 4.29-4.33 (2H, m), 4.10-4.16 (6H, m), 2.98-3.04 (2H, m), 1.90-2.10 (2H, m), 1.31 (9H, s)

Mass spectrometry value (ESI-MS, m/z): 549 (M⁺+1)

Example 76 3-{[4-(Tert-butyl)phenyl]sulfanyl}-propyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)-oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (77 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (125 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[4-(tert-butyl)phenyl]sulfanyl-1-propanol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 47%).

¹H-NMR (CDCl₃, 400 MHz): 8.80 (1H, s), 8.33-8.38 (1H, m), 8.07 (1H, bs), 7.15-7.62 (8H, m), 4.35 (2H, t, J=6.2 Hz), 4.18 (3H, s), 4.12 (3H, s), 3.02 (2H, t, J=7.1 Hz), 2.00-2.08 (2H, m), 1.31 (9H, s)

Mass spectrometry value (ESI-MS, m/z): 583 (M⁺+1)

Example 77 3-[(4-Chloro-2-methylphenyl)sulfanyl]-propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (73 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[4-chloro-2-methylphenyl]sulfanyl-1-propanol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (98 mg, yield 69%).

¹H-NMR (CDCl₃, 400 MHz): 8.45-8.50 (3H, m), 8.15 (1H, s), 7.57-7.65 (3H, m), 7.12-7.25 (5H, m), 6.82 (1H, s), 6.69 (1H, d, J=6.6 Hz), 4.33 (2H, t, J=6.2 Hz), 4.17 (3H, s), 4.10 (3H, s), 2.99 (2H, t, J=7.2 Hz), 2.37 (3H, s), 1.95-2.08 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 540 (M⁺+1)

Example 78 3-[(4-Chloro-2-methylphenyl)sulfanyl]-propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (82 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[4-chloro-2-methylphenyl]sulfanyl-1-propanol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 58%).

¹H-NMR (CDCl₃, 400 MHz): 8.43-8.50 (1H, m), 8.16 (1H, s), 7.66-7.76 (2H, m), 7.00-7.25 (5H, m), 6.55 (1H, d, J=6.6 Hz), 6.46 (1H, s), 4.33 (2H, t, J=6.2 Hz), 4.17 (3H, s), 4.11 (3H, s), 2.96-3.03 (2H, m), 2.37 (3H, s), 2.27 (3H, s), 2.11 (3H, s), 1.98-2.10 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 79 3-[(4-Chloro-2-methylphenyl)sulfanyl]-propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[4-chloro-2-methylphenyl]sulfanyl-1-propanol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (81 mg, yield 49%).

¹H-NMR (CDCl₃, 400. MHz): 8.42-8.48 (1H, m), 8.12 (1H, s), 7.86 (1H, s), 7.62 (1H, s), 7.08-7.23 (3H, m), 6.94 (1H, s), 6.56 (1H, d, J=6.6 Hz), 6.43 (1H, s), 4.31 (2H, t, J=6.2 Hz), 4.15 (3H, s), 4.08 (3H, s), 2.97 (2H, t, J=7.2 Hz), 2.35 (3H, s), 2.26 (3H, s), 2.11 (3H, s), 1.96-2.06 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 568 (M⁺+1)

Example 80 3-[(4-Chloro-2-methylphenyl)sulfanyl]-propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (88 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[4-chloro-2-methylphenyl]sulfanyl-1-propanol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 45%).

¹H-NMR (CDCl₃, 400 MHz): 8.73 (1H, s), 7.85 (1H, bs), 7.60 (1H, s), 7.51-7.57 (2H, m), 7.10-7.24 (5H, m), 6.74 (5H, m), 4.32 (2H, t, J=6.1 Hz), 4.15 (3H, s), 4.11 (3H, s), 2.98 (2H, t, J=7.2 Hz), 2.37 (3H, s), 1.98-2.07 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 541 (M⁺+1)

Example 81 3-[(4-chloro-2-methylphenyl)sulfanyl]-propyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)-oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (75 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-[4-chloro-2-methylphenyl]sulfanyl-1-propanol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (69 mg, yield 50%).

¹H-NMR (CDCl₃, 400 MHz): 8.66 (1H, s), 8.23-8.33 (1H, m), 7.53 (1H, s), 7.46 (1H, s), 7.34 (1H, d, J=2.7 Hz), 7.12-7.25 (5H, m), 4.34 (2H, t, J=7.1 Hz), 4.09 (3H, s), 4.08 (3H, s), 3.00 (2H, t, J=7.1 Hz), 2.37 (3H, s), 2.00-2.08 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 575 (M⁺+1)

Example 82 3-(Trifluoromethyl)phenethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (72 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (125 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-trifluoromethylphenethyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (101 mg, yield 76%).

¹H-NMR (CDCl₃, 400 MHz): 8.42-8.49 (1H, m), 8.12 (1H, s), 7.61 (1H, s), 7.42-7.59 (6H, m), 7.13-7.18 (2H, m), 6.76 (1H, s), 6.66 (1H, d, J=6.6 Hz), 4.44 (2H, t, J=6.7 Hz), 4.15 (3H, s), 4.08 (3H, s), 3.07 (2H, t, J=6.7 Hz)

Mass spectrometry value (ESI-MS, m/z): 513 (M⁺+1)

Example 83 3-(Trifluoromethyl)phenethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (68 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (125 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-trifluoromethylphenethyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 73%).

¹H-NMR (CDCl₃, 400 MHz): 8.4-8.49 (1H, m), 8.16 (1H, s), 7.67 (1H, s), 7.40-7.56 (5H, m), 7.02 (1H, d, J=8.8 Hz), 6.54 (1H, d, J=6.4 Hz), 6.42 (1H, bs), 4.46 (2H, t, J=6.7 Hz), 4.17 (3H, s), 4.11 (3H, s), 3.09 (2H, t, J=6.7 Hz), 2.23 (3H, s), 2.10 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 541 (M⁺+1)

Example 84 3-(Trifluoromethyl)phenethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (125 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-trifluoromethylphenethyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (79 mg, yield 56%).

¹H-NMR (CDCl₃, 400 MHz): 8.13-8.62 (2H, m), 7.26-8.00 (6H, m), 6.96 (1H, s), 6.64-6.28 (1H, m), 6.42 (1H, bs), 4.46 (2H, t, J=6.7 Hz), 4.03-4.18 (6H, m), 3.07-3.13 (3H, m), 2.23-2.30 (3H, m), 2.11 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 541 (M⁺+1)

Example 85 3-(Trifluoromethyl)phenethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (82 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (125 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-trifluoromethylphenethyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 45%).

¹H-NMR (CDCl₃, 400 MHz): 8.76 (1H, s), 8.01 (1H, s), 7.60 (1H, s), 7.43-7.58 (6H, m), 7.17-7.24 (2H, m), 6.79 (1H, s), 4.44 (2H, t, J=6.7 Hz), 4.17 (3H, s), 4.11 (3H, s), 3.08 (2H, t, J=6.8 Hz)

Mass spectrometry value (ESI-MS, m/z): 514 (M⁺+1)

Example 86 3-(Trifluoromethyl)phenethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (85 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (125 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-trifluoromethylphenethyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (69 mg, yield 46%).

¹H-NMR (CDCl₃, 400 MHz): 8.79 (1H, s), 8.27-8.34 (1H, m), 8.03 (1H, s), 7.30-7.62 (6H, m), 7.24-7.23 (2H, m), 4.46 (2H, t, J=6.8 Hz), 4.18 (3H, s), 4.11 (3H, s), 3.10 (2H, t, J=6.9 Hz)

Mass spectrometry value (ESI-MS, m/z): 549 (M⁺+1)

Example 87 1-[3-(Trifluoromethyl)phenyl]ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (74 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (115 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-trifluoromethyl-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (81 mg, yield 59%).

¹H-NMR (CDCl₃, 400 MHz): 8.41-8.48 (1H, m), 8.11 (1H, s), 7.45-7.68 (7H, m), 7.13-7.18 (2H, m), 6.93 (1H, s), 6.65 (1H, d, J=6.6 Hz), 5.94 (1H, q, J=6.6 Hz), 4.14 (3H, s), 4.08 (3H, s), 1.63 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 513 (M⁺+1)

Example 88 1-[3-(Trifluoromethyl)phenyl]ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (72 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (110 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-trifluoromethyl-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (90 mg, yield 68%).

¹H-NMR (CDCl₃, 400 MHz): 8.39-8.45 (1H, m), 8.13 (1H, s), 7.40-7.72 (6H, m), 6.99 (1H, d, J=9.0 Hz), 6.48-6.55 (2H, m), 5.93 (1H, 1, J=6.6 Hz), 4.15 (3H, s), 4.09 (3H, s), 2.24 (3H, s), 2.07 (3H, s), 1.63 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 542 (M⁺+1)

Example 89 1-[3-(Trifluoromethyl)phenyl]ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (76 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (110 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-trifluoromethyl-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (78 mg, yield 58%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.47 (1H, m), 8.12 (1H, s), 7.84 (1H, s), 7.45-7.68 (5H, m), 6.93 (1H, s), 6.47-6.57 (2H, m), 5.93 (1H, q, J=6.8 Hz), 4.14 (3H, s), 4.08 (3H, s), 2.27 (3H, s), 2.09 (3H, s), 1.63 (3H, d, J=6.8 Hz)

Mass spectrometry value (ESI-MS, m/z): 542 (M⁺+1)

Example 90 1-[3-(Trifluoromethyl)phenyl]ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (89 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-trifluoromethyl-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 48%).

¹H-NMR (CDCl₃, 400 MHz): 8.75 (1H, s), 8.07 (1H, s), 7.14-7.63 (8H, m), 6.95 (1H, s), 6.79 (1H, d, J=8.8 Hz), 5.93 (1H, q, J=6.6 Hz), 4.15 (3H, s), 4.09 (3H, s), 1.61 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 514 (M⁺+1)

Example 91 1-[3-(Trifluoromethyl)phenyl]ethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (76 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-trifluoromethyl-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (53 mg, yield 39%).

¹H-NMR (CDCl₃, 400 MHz): 8.76 (1H, s), 7.86 (1H, s), 7.20-7.65 (6H, m), 6.88-6.92 (2H, m), 6.72-6.77 (1H, m), 5.87-5.95 (1H, m), 4.15 (3H, s), 4.09 (3H, s), 1.60 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 549 (M⁺+1)

Example 92 1-(2,4,5-Trifluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (87 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (130 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2,4,5-trifluoro-α-methylbenzyl alcohol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 49%).

¹H-NMR (CDCl₃, 400 MHz): 8.41-8.49 (1H, m), 8.11 (1H, s), 7.56-7.64 (4H, m), 7.12-7.20 (2H, m), 6.80-6.72 (2H, m), 6.65 (1H, d, J=6.4 Hz), 6.07 (1H, q, J=6.4 Hz), 4.14 (3H, s), 4.08 (3H, s), 1.59 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 499 (M⁺+1)

Example 93 1-(2,4,5-Trifluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (76 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (130 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2,4,5-trifluoro-α-methylbenzyl alcohol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 46%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.47 (1H, m), 8.13 (1H, s), 7.62-7.74 (2H, m), 6.82-6.72 (3H, m), 6.48-6.55 (2H, m), 6.07 (1H, q, J=6.6 Hz), 4.15 (3H, s), 4.09 (3H, s), 2.26 (3H, s), 2.08 (3H, s), 1.59 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 528 (M⁺+1)

Example 94 1-(2,4,5-Trifluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (82 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (130 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2,4,5-trifluoro-α-methylbenzyl alcohol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 48%).

¹H-NMR (CDCl₃, 400 MHz): 8.4-8.48 (1H, m), 8.11 (1H, s), 7.84 (1H, s), 7.61 (1H, s), 6.80-7.30 (3H, m), 6.52-6.57 (2H, m), 6.06 (1H, q, J=6.7 Hz), 4.14 (3H, s), 4.08 (3H, s), 2.28 (3H, s), 2.09 (3H, s), 1.59 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 527 (M⁺+1)

Example 95 1-(2,4,5-Trifluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (89 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (130 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2,4,5-trifluoro-α-methylbenzyl alcohol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (51 mg, yield 32%).

¹H-NMR (CDCl₃, 400 MHz): 8.73 (1H, s), 8.05 (1H, s), 7.58 (1H, s), 7.53-7.58 (1H, m), 6.50-7.25 (6H, m), 6.00-6.10 (1H, m), 4.15 (3H, s), 4.09 (3H, s), 1.57 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 500 (M⁺+1)

Example 96 1-(2,4,5-Trifluorophenyl)ethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (130 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2,4,5-trifluoro-α-methylbenzyl alcohol (80 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 35%).

¹H-NMR (CDCl₃, 400 MHz): 8.72 (1H, s), 8.27 (1H, d, J=9.0 Hz), 7.99 (1H, s), 7.50 (1H, s), 6.80-7.28 (5H, m), 5.95-6.08 (1H, m), 4.11 (3H, s), 4.04 (3H, s), 1.56 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 535 (M⁺+1)

Example 97 1-(3-Fluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (97 mg) was added to toluene/triethylamine=10/1 (10 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (150 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-fluoro-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (111 mg, yield 68%).

¹H-NMR (CDCl₃, 400 MHz): 8.41-8.47 (1H, m), 8.12 (1H, s), 7.55-7.62 (3H, m), 6.86-7.38 (7H, m), 6.65 (1H, d, J=6.6 Hz), 5.88 (1H, 1, J=6.6 Hz), 4.14 (3H, s), 4.08 (3H, s), 1.60 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 463 (M⁺+1)

Example 98 1-(3-Fluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (86 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (150 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-fluoro-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (89 mg, yield 64%).

¹H-NMR (CDCl₃, 400 MHz): 8.38-8.44 (1H, m), 8.13 (1H, s), 7.66-7.75 (1H, m), 7.64 (1H, s), 6.95-7.36 (6H, m), 6.51 (1H, d, J=6.4 Hz), 5.87 (1H, q, J=6.6 Hz), 4.15 (3H, s), 4.09 (3H, s), 2.25 (3H, s), 2.07 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 99 1-(3-Fluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (97 mg) was added to toluene/triethylamine=10/1 (10 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (150 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-fluoro-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (108 mg, yield 68%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.45 (1H, m), 8.12 (1H, s), 7.87 (1H, s), 7.62 (1H, s), 6.90-7.38 (5H, m), 6.54 (1H, d, J=6.8 Hz), 6.49 (1H, s), 4.15 (3H, s), 4.08 (3H, s), 2.27 (3H, s), 2.09 (3H, s), 1.61 (3H, d, J=6.8 Hz)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 100 1-(3-Fluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (99 mg) was added to toluene/triethylamine=10/1 (10 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (150 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-fluoro-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 36%).

¹H-NMR (CDCl₃, 400 MHz): 8.75 (1H, s), 7.98 (1H, bs), 8.47 (1H, bs), 6.48-7.60 (9H, m), 5.82-5.90 (1H, m), 4.13 (3H, s), 4.08 (3H, s), 1.58 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 464 (M⁺+1)

Example 101 1-(3-Fluorophenyl)ethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (98 mg) was added to toluene/triethylamine=10/1 (10 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (150 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-fluoro-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (49 mg, yield 31%).

¹H-NMR (CDCl₃, 400 MHz): 8.78 (1H, s), 8.34 (1H, d, J=9.3 Hz), 8.13 (1H, s), 7.56 (1H, s), 6.97-7.38 (7H, m), 5.88 (1H, q, J=6.5 Hz), 4.17 (3H, s), 4.17 (3H, s), 4.10 (3H, s), 1.61 (3H, d, J=6.8 Hz)

Mass spectrometry value (ESI-MS, m/z): 499 (M⁺+1)

Example 102 1-(4-Fluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (8.0 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluoro-α-methylbenzyl alcohol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (91 mg, yield 73%).

¹H-NMR (CDCl₃, 400 MHz): 8.43-8.48 (1H, m), 8.14 (1H, s), 7.63 (1H, s), 7.57-7.61 (2H, m), 7.37-7.42 (2H, m), 7.14-7.19 (2H, m), 7.04-7.10 (2H, m), 6.86 (1H, s), 6.66 (1H, d, J=6.6 Hz), 5.90 (1H, q, J=6.6 Hz), 4.16 (3H, s), 4.10 (3H, s), 1.62 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 461 (M⁺+1)

Example 103 1-(4-Fluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (86 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (117 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluoro-α-methylbenzyl alcohol (55 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (94 mg, yield 72%).

¹H-NMR (CDCl₃, 400 MHz): 8.42-8.48 (1H, m), 8.15 (1H, s), 7.74 (1H, d, J=8.5 Hz), 7.66 (1H, s), 7.37-7.43 (2H, m), 6.98-7.10 (3H, m), 6.48-6.55 (2H, m), 5.90 (1H, q, J=6.6 Hz), 4.17 (3H, s), 4.10 (3H, s), 2.25 (3H, s), 2.09 (3H, s), 1.63 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 104 1-(4-Fluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (123 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluoro-α-methylbenzyl alcohol (58 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (87 mg, yield 64%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.48 (1H, m), 8.12 (1H, s), 7.88 (1H, s), 7.61 (1H, s), 7.30-7.41 (2H, m), 7.30-7.41 (2H, m), 7.00-7.10 (2H, m), 6.91 (1H, s), 6.53 (1H, d, J=6.6 Hz), 6.45 (1H, s), 5.87 (1H, q, J=6.7 Hz), 4.14 (3H, s), 4.08 (3H, s), 2.25 (3H, s), 2.09 (3H, s), 1.61 (3H, d, J=6.7 Hz)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 105 1-(4-Fluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluoro-α-methylbenzyl alcohol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (59 mg, yield 47%).

¹H-NMR (CDCl₃, 400 MHz): 8.77 (1H, s), 8.08 (1H, s), 7.60 (1H, s), 7.52-7.58 (2H, m), 7.36-7.41 (2H, m), 7.16-7.20 (2H, m), 7.02-7.09 (2H, m), 6.79 (1H, s), 5.89 (1H, q.J=6.6 Hz), 4.18 (3H, s), 4.11 (3H, s), 1.61 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 464 (M⁺+1)

Example 106 1-(4-Fluorophenyl)ethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (85 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (114 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluoro-α-methylbenzyl alcohol (54 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (45 mg, yield 35%).

¹H-NMR (CDCl₃, 400 MHz): 8.80 (1H, s), 8.35 (1H, d, J=9.0 Hz), 8.12 (1H, s), 7.57 (1H, s), 7.05-7.44 (7H, m), 5.90 (1H, q, J=6.6 Hz), 4.19 (3H, s), 4.11 (3H, s), 1.63 (3H, d, J=6.8 Hz)

Mass spectrometry value (ESI-MS, m/z): 499 (M⁺+1)

Example 107 4-Methylbenzyl {4-[(6,7-dimethoxy-4-quinolyl)oxy]anilino}methanethioate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (82 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methylbenzylmercaptan (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (90 mg, yield 65%).

¹H-NMR (CDCl₃, 400 MHz): 8.43-8.50 (1H, m), 8.13 (1H, s), 7.55-7.72 (4H, m), 7.00-7.26 (6H, m), 6.67 (1H, d, J=6.4 Hz), 4.21 (2H, s), 4.16 (3H, s), 4.10 (3H, s), 2.33 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 462 (M⁺+1)

Example 108 4-Methylbenzyl {4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylanilino}methanethioate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (145 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methylbenzylmercaptan (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (87 mg, yield 60%).

¹H-NMR (CDCl₃, 400 MHz): 8.47 (1H, bs), 8.16 (1H, s), 7.58-7.70 (2H, m), 6.88-7.26 (6H, m), 6.6 (1H, bs), 4.21 (2H, s), 4.17 (3H, s), 4.11 (3H, s), 2.34 (3H, s), 2.27 (3H, s), 2.14 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 490 (M⁺+1)

Example 109 4-Methylbenzyl {4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylanilino}methanethioate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (145 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methylbenzylmercaptan (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (74 mg, yield 54%).

¹H-NMR (CDCl₃, 400 MHz): 8.45-8.52 (1H, m), 8.15 (1H, s), 7.80 (1H, s), 7.64 (1H, s), 6.89-7.28 (6H, m), 6.57 (1H, d, J=6.3 Hz), 4.22 (2H, s), 4.17 (3H, s), 4.11 (3H, s), 2.34 (3H, s), 2.28 (3H, s), 2.13 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 490 (M⁺+1)

Example 110 4-Methylbenzyl {4-[(6,7-dimethoxy-4-quinazolinyl)oxy]anilino}methanethioate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (81 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methylbenzylmercaptan (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (74 mg, yield 54%).

¹H-NMR (CDCl₃, 400 MHz): 8.72 (1H, s), 8.12 (1H, s), 7.50-7.67 (4H, m), 7.10-7.26 (6H, m), 4.21 (2H, s), 4.18 (3H, s), 4.12 (3H, s), 2.33 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 462 (M⁺+1)

Example 111 4-Methylbenzyl {2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]anilino}methanethioate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (85 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methylbenzylmercaptan (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (58 mg, yield 42%).

¹H-NMR (CDCl₃, 400 MHz): 8.81 (1H, s), 8.44 (1H, d, J=9.3 Hz), 8.13 (1H, s), 7.52-7.55 (2H, m), 7.11-7.34 (6H, m), 4.24 (2H, s), 4.19 (3H, s), 4.12 (3H, s), 2.34 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 112 1-(2-Bromophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7′-Dimethoxy-4-quinolyl)oxy]aniline (88 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (145 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-bromo-α-methylbenzyl alcohol (90 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (89 mg, yield 54%).

¹H-NMR (CDCl₃, 400 MHz): 8.44 (1H, d, J=6.7 Hz), 8.12 (1H, s), 6.90-7.61 (10H, m), 6.65 (1H, d, J=6.7 Hz), 6.20 (1H, q, J=6.4 Hz), 4.14 (3H, s), 4.08 (3H, s), 1.59 (3H, d, J=6.4 Hz)

Mass spectrometry value (ESI-MS, m/z): 524 (M⁺+1)

Example 113 1-(2-Bromophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (78 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (145 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-bromo-α-methylbenzyl alcohol (90 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (101 mg, yield 71%).

¹H-NMR (CDCl₃, 400 MHz): 8.43 (1H, dd, J=6.5 Hz), 8.15 (1H, s), 7.15-7.7.8 (6H, m), 7.00 (1H, d, J=8.8 Hz), 6.57 (1H, bs), 6.52 (1H, d, J=6.5 Hz), 6.21 (1H, q, J=6.5 Hz), 4.17 (3H, s), 4.11 (3H, s), 2.28 (3H, s), 2.09 (3H, s), 1.62 (3H, d, J=6.5 Hz)

Mass spectrometry value (ESI-MS, m/z): 552 (M⁺+1)

Example 114 1-(2-Bromophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (85 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (148 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-bromo-α-methylbenzyl alcohol (90 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (70 mg, yield 45%).

¹H-NMR (CDCl₃, 400 MHz): 8.45 (1H, dd, J=6.6 Hz), 8.14 (1H, s), 7.92 (1H, bs), 7.15-7.65 (6H, m), 6.94 (1H, s), 6.46-6.58 (2H, m), 6.22 (1H, q, J=6.6 Hz), 4.17 (3H, s), 4.10 (3H, s), 2.30 (3H, s), 2.10 (3H, s), 1.63 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 552 (M⁺+1)

Example 115 1-(2-Bromophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-bromo-α-methylbenzyl alcohol (90 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 35%).

¹H-NMR (CDCl₃, 400 MHz): 8.75 (1H, s), 8.04 (1H, s), 7.14-7.61 (9H, m), 6.94 (1H, bs), 6.20 (1H, q, J=6.5 Hz), 4.17 (3H, s), 4.11 (3H, s), 1.60 (3H, d, J=6.5 Hz)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 116 1-(2-Bromophenyl)ethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (85 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (139 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-bromo-α-methylbenzyl alcohol (90 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (51 mg, yield 33%).

¹H-NMR (CDCl₃, 400 MHz): 8.80 (1H, s), 8.38 (1H, d, J=9.3 Hz), 8.14 (1H, s), 7.16-7.60 (7H, m), 6.23 (1H, q, J=6.6 Hz), 4.19 (3H, s), 4.11 (3H, s), 1.63 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 560 (M⁺+1)

Example 117 1-(3-Bromophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (72 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (111 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-bromo-α-methylbenzyl alcohol (75 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (79 mg, yield 584%).

¹H-NMR (CDCl₃, 400 MHz): 8.46 (1H, dd, J=6.4 Hz) 8.13 (1H, s), 7.16-7.64 (9H, m), 7.01 (1H, s), 6.68 (1H, d, J=6.4 Hz), 5.86 (1H, q, J=6.4 Hz), 4.16 (3H, s), 4.10 (3H, s), 1.61 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 524 (M⁺+1)

Example 118 1-(3-Bromophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (68 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-bromo-α-methylbenzyl alcohol (75 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (83 mg, yield 67%).

¹H-NMR (CDCl₃, 400 MHz): 8.45 (1H, dd, J=6.6 Hz), 8.15 (1H, s like), 7.16-7.74 (7H, m), 7.02 (1H, d, J=9.0 Hz), 6.54 (1H, d, J=6.1 Hz), 5.86 (1H, q, J=6.6 Hz), 4.17 (3H, s), 4.11 (3H, s), 2.27 (3H, s), 2.10 (3H, s), 1.62 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 552 (M⁺+1)

Example 119 1-(3-Bromophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (88 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (138 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-bromo-α-methylbenzyl alcohol (75 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 55%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.50 (1H, m), 8.15 (1H, s like), 7.89 (1H, bs), 7.20-7.66 (5H, m), 6.95 (1H, s), 6.56 (1H, d, J=6.4 Hz), 6.50 (1H, bs), 5.86 (1H, q, J=6.6 Hz), 4.17 (3H, s), 4.10 (3H, s), 2.30 (3H, s), 2.11 (3H, s), 1.62 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 552 (M⁺+1)

Example 120 1-(3-Bromophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (74 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (125 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-bromo-α-methylbenzyl alcohol (75 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 44%).

¹H-NMR (CDCl₃, 400 MHz): 8.76 (1H, s), 8.06 (1H, s), 7.16-7.62 (8H, m), 6.85 (1H, bs), 5.85 (1H, q, J=6.6 Hz), 4.18 (3H, s), 4.11 (3H, s), 1.65 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 121 1-(3-Bromophenyl)ethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (76 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (119 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-bromo-α-methylbenzyl alcohol (75 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (51 mg, yield 40%).

¹H-NMR (CDCl₃, 400 MHz): 8.80 (1H, s), 8.35 (1H, d, J=9.0 Hz), 8.12 (1H, s), 7.54-7.60 (2H, m), 7.44-7.58 (1H, m), 7.15-7.36 (4H, m), 5.86 (1H, q, J=6.7 Hz), 4.19 (3H, s), 4.16 (3H, s, 1.63 (3H, d, J=6.7 Hz)

Mass spectrometry value (ESI-MS, m/z): 560 (M⁺+1)

Example 122 1-(2-Fluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (77 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (117 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-fluoro-α-methylbenzyl alcohol (55 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (101 mg, yield 78%).

Mass spectrometry value (ESI-MS, m/z): 524 (M⁺+1)

Example 123 1-(2-Fluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (74 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (103 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-fluoro-α-methylbenzyl alcohol (55 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 73%).

¹H-NMR (CDCl₃, 400 MHz): 8.37 (1H, dd, J=6.6 Hz), 8.08 (1H, s like), 7.67 (1H, d, J=8.1 Hz), 7.59 (1H, s), 7.37 (1H, dd, J=7.1 Hz), 7.10 (1H, dd, J=7.4 Hz), 7.01 (1H, dd, J=9.4 Hz), 6.93 (1H, d, J=8.8 Hz), 6.50 (1H, s), 6.46 (1H, d, J=6.6 Hz), 6.10 (1H, q, J=6.6 Hz), 4.10 (3H, s), 4.04 (3H, s), 2.22 (3H, s), 2.02 (3H, s), 1.59 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 124 1-(2-Fluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (71 mg) was added toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (99 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-fluoro-α-methylbenzyl alcohol (55 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (78 mg, yield 68%).

¹H-NMR (CDCl₃, 400 MHz): 8.45 (1H, dd, J=6.5 Hz), 8.15 (1H, d, J=4.2 Hz), 7.91 (1H, s), 7.64 (1H, s), 7.42-7.45 (1H, m), 7.28-7.33 (1H, m), 7.06-7.11 (1H, m), 7.15-7.20 (1H, m), 6.94 (1H, s), 6.56 (1H, d, J=6.5 Hz), 6.52 (1H, s), 6.17 (1H, q, J=6.7 Hz) 4.17 (3H, s), 4.10 (3H, s), 2.29 (3H, s), 2.11 (3H, s), 1.66 (3H, d, J=6.7 Hz)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 125 1-(2-Fluorophenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (136 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-fluoro-α-methylbenzyl alcohol (55 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (79 mg, yield 52%).

¹H-NMR (CDCl₃, 400 MHz): 8.74 (1H, s), 8.06 (1H, s), 7.58 (1H, s), 7.54 (2H, d, J=9.0 Hz), 7.39-7.43 (1H, m), 7.23-7.32 (1H, m), 7.12-7.17 (3H, m), 7.03-7.08 (1H, m), 6.86 (1H, s), 6.14 (1H, q, J=6.6 Hz), 4.15 (3H, s), 4.09 (3H, s), 1.62 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 464 (M⁺+1)

Example 126 1-(2-Fluorophenyl)ethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]aniline (83 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (134 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-fluoro-α-methylbenzyl alcohol (55 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 45%).

¹H-NMR (CDCl₃, 400 MHz): 8.80 (1H, s), 8.37 (1H, d, J=9.2 Hz), 8.15 (1H, s), 7.58 (1H, s), 7.43-7.52 (1H, m), 7.32 (1H, d, J=2.7° Hz), 7.28-7.35 (1H, m), 7.15-7.20 (2H, m), 7.06-7.11 (1H, m), 6.19 (1H, q, J=6.6 Hz), 4.19 (3H, s), 4.12 (3H, s), 1.66 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI MS, m/z): 499 (M⁺+1)

Example 127 1-(2-Ethoxyphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (122 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-ethoxy-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (98 mg, yield 69%).

¹H-NMR (CDCl₃, 400 MHz): 8.46 (1H, dd, J=6.5 Hz), 8.14 (1H, s like), 7.58-7.64 (3H, m), 7.38-7.42 (1H, m), 7.16-7.18 (2H, m), 6.85-7.00 (3H, m), 6.68 (1H, d, J=6.6 Hz), 6.31 (1H, q, J=6.5 Hz), 4.16 (3H, s), 4.10 (3H, s), 4.05-4.13 (2H, m), 1.59 (3H, d, J=6.5 Hz), 1.44 (3H, t, J=7.1 Hz)

Mass spectrometry value (ESI-MS, m/z): 490 (M⁺+1)

Example 128 1-(2-Ethoxyphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (72 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (100 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-ethoxy-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (71 mg, yield 58%).

¹H-NMR (CDCl₃, 400 MHz): 8.42 (1H, d, J=6.5 Hz), 8.13 (1H, s like), 7.73-7.80 (1H, m), 7.64 (1H, s), 7.10-7.40 (2H, m), 6.80-7.00 (3H, m), 6.48-6.53 (1H, m), 6.28 (1H, q, J=6.4 Hz), 4.15 (3H, s), 4.09 (3H, s), 4.02-4.10 (2H, m), 2.24 (3H, s), 2.07 (3H, s), 1.57 (3H, d, J=6.4 Hz), 1.42 (3H, t, J=6.9 Hz)

Mass spectrometry value (ESI-MS, m/z): 518 (M⁺+1)

Example 129 1-(2-Ethoxyphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (83 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (115 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-ethoxy-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (78 mg, yield 55%).

¹H-NMR (CDCl₃, 400 MHz): 8.42 (1H, dd, J=6.3 Hz), 8.13 (1H, s like), 7.93 (1H, bs), 7.38 (1H, d, J=7.6 Hz), 6.83-6.99 (4H, m), 6.53-6.58 (1H, m), 6.49 (1H, bs), 6.29 (1H, q, J=6.5 Hz), 4.15 (3H, s), 4.08 (3H, s), 4.04-4.11 (2H, m), 2.27 (3H, s), 2.08 (3H, s), 1.58 (3H, d, J=6.5 Hz), 1.43 (3H, t, J=6.9 Hz)

Mass spectrometry value (ESI-MS, m/z): 518 (M⁺+1)

Example 130 1-(2-Ethoxyphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (77 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (117 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-ethoxy-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (63 mg, yield 46%).

¹H-NMR (CDCl₃, 400 MHz): 8.74 (1H, s like), 8.05 (1H, s), 7.53-7.59 (3H, m), 7.34-7.38 (1H, m), 7.13-7.26 (3H, m), 6.82-6.98 (3H, m), 6.27 (1H, q, J=6.5 Hz), 4.15 (3H, s), 4.09 (3H, s), 4.02-4.10 (2H, m), 1.56 (3H, d, J=6.5 Hz), 1.42 (3H, t, J=7.0 Hz)

Mass spectrometry value (ESI-MS, m/z): 491 (M⁺+1)

Example 131 1-(2-Ethoxyphenyl)ethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (80 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (109 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-ethoxy-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (58 mg, yield 43%).

¹H-NMR (CDCl₃, 400 MHz): 8.80 (1H, s), 8.40 (1H, d, J=9.0 Hz), 8.13 (1H, s), 7.58 (1H, s), 7.14-7.45 (4H, m), 6.86-7.01 (3H, m), 6.32 (1H, q, J=6.3 Hz), 4.19 (3H, s), 4.12 (3H, s), 4.05-4.13 (2H, m), 1.61 (3H, d, J=6.3 Hz), 1.39-1.45 (3H, m)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 132 1-(4-Methylphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (72 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (109 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methyl-α-methylbenzyl alcohol (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (98 mg, yield 81%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.45 (1H, m), 8.11 (1H, s), 7.61 (1H, s), 7.53-7.59 (2H, m), 7.10-7.32 (6H, m), 6.78-6.85 (1H, m), 6.65 (1H, d, J=6.6 Hz), 5.87 (1H, q, J=6.6 Hz), 4.14 (3H, s), 4.08 (3H, s), 2.34 (3H, s), 1.60 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 460 (M⁺+1)

Example 133 1-(4-Methylphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (111 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methyl-α-methylbenzyl alcohol (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (97 mg, yield 75%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.45 (1H, m), 8.12 (1H, s), 7.73 (1H, d, J=8.3 Hz), 7.64 (1H, s), 7.15-7.32 (4H, m), 6.97 (1H, d, J=8.8 Hz), 6.51 (1H, d, J=6.6 Hz), 6.48 (1H, s), 5.87 (1H, q, J=6.5 Hz), 4.14 (3H, s), 4.08 (3H, s), 2.34 (3H, s), 2.22 (3H, s), 2.06 (3H, s), 1.60 (3H, d, J=6.4 Hz)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 134 1-(4-Methylphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (111 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methyl-α-methylbenzyl alcohol (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 68%).

¹H-NMR (CDCl₃, 400 MHz): 8.41-8.47 (1H, m), 8.12 (1H, s), 7.90 (1H, s), 7.62 (1H, s), 7.15-7.33 (4H, m), 6.91 (1H, s), 6.54 (1H, d, J=6.4 Hz), 6.45 (1H, s), 5.87 (1H, q, J=6.6 Hz), 4.14 (3H, s), 4.08 (3H, s), 2.34 (3H, s), 2.22 (3H, s), 2.08 (3H, s), 1.61 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 135 1-(4-Methylphenyl)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (76 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (115 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methyl-α-methylbenzyl alcohol (52 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (85 mg, yield 67%).

¹H-NMR (CDCl₃, 400 MHz): 8.74 (1H, s), 8.03 (1H, s), 7.43-7.60 (3H, m), 6.74-7.30 (6H, m), 6.45 (1H, bs), 5.80-5.90 (1H, m), 4.14 (3H, s), 4.09 (3H, s), 2.33 (3H, s), 1.59 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 461 (M⁺+1)

Example 136 1-(4-Methylphenyl)ethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (78 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (106 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-methyl-α-methylbenzyl alcohol (48 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 49%).

¹H-NMR (CDCl₃, 400 MHz): 8.78 (1H, s), 8.35 (1H, d, J=9.0 Hz), 8.12 (1H, s), 7.55 (1H, s), 7.12-7.34 (7H, m), 5.83-5.91 (1H, m), 4.17 (3H, s), 4.09 (3H, s), 2.34 (3H, s), 1.62 (3H, d, J=6.5 Hz)

Mass spectrometry value (ESI-MS, m/z): 405 (M⁺+1)

Example 137 3-[(4-Methylphenyl)sulfanyl]ethyl N-{4-[(dimethoxy-4-quinolyl)oxy]-phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (78 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (118 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-[(4-methylphenyl)sulfanyl]-1-ethanol (66 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 35%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.49 (1H, M), 8.13 (1H, s), 7.62 (1H, s), 7.55 (1H, d, J=9.0 Hz), 7.09-7.35 (6H, m), 6.75 (1H, s), 6.66 (1H, d, J=6.4 Hz), 4.33 (2H, t, J=6.4 Hz), 4.15 (3H, s), 4.08 (3H, s), 3.15 (2H, t, J=6.4 Hz), 2.31 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 138 3-[(4-Methylphenyl)sulfanyl]ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (72 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (100 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-[(4-methylphenyl)sulfanyl]-1-ethanol (56 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (53 mg, yield 43%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.46 (1H, m), 8.13 (1H, s), 7.63-7.74 (2H, m), 6.98-7.36 (5H, m), 5.53 (1H, d, J=6.6 Hz), 6.43 (1H, s), 4.33 (2H, t, J=6.7 Hz), 4.15 (3H, s), 4.09 (3H, s), 3.16 (2H, t, J=6.7 Hz), 2.30 (6H, s), 2.23 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 520 (M⁺+1)

Example 139 3-[(4-Methylphenyl)sulfanyl]ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (74 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (103 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-[(4-methylphenyl)sulfanyl]-1-ethanol (58 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (51 mg, yield 40%).

¹H-NMR (CDCl₃, 400 MHz): 8.41-8.48 (1H, m), 8.13 (1H, s), 7.85 (1H, s), 7.62 (1H, s), 6.92-7.35 (5H, m), 6.55 (1H, d, J=6.1 Hz), 6.39 (1H, s), 4.33 (1H, t, J=6.7 Hz), 4.15 (3H, s), 4.08 (3H, s), 3.16 (2H, t, J=6.7 Hz), 2.31 (3H, s), 2.24 (3H, s), 2.14 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 520 (M⁺+1)

Example 140 3-[(4-Methylphenyl)sulfanyl]ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (69 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (105 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-[(4-methylphenyl)sulfanyl]-1-ethanol (59 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (29 mg, yield 24%).

¹H-NMR (CDCl₃, 400 MHz): 8.76 (1H, s), 8.10 (1H, s), 7.59 (1H, s), 7.49-7.56 (2H, m), 6.70-7.33 (7H, m), 4.32 (2H, t, J=6.7 Hz), 4.17 (3H, s), 4.10 (3H, s), 3.14 (2H, t, J=6.7 Hz), 2.31 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 493 (M⁺+1).

Example 141 3-[(4-Methylphenyl)sulfanyl]ethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (75 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (102 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-[(4-methylphenyl)sulfanyl]-1-ethanol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (57 mg, yield 30%).

¹H-NMR (CDCl₃, 400 MHz): 8.79 (1H, s), 8.32 (1H, d, J=9.3 Hz), 8.13 (1H, s), 7.56 (1H, s), 7.08-7.36 (7H, m), 4.35 (2H, t, J=6.7 Hz), 4.18 (3H, s), 4.10 (3H, s), 3.16 (2H, t, J=6.7 Hz), 2.30 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 527 (M⁺+1)

Example 142 3-(2-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (70 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (106 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-fluorophenoxy)-1-propanol (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 55%).

¹H-NMR (CDCl₃, 400 MHz): 8.44-8.47 (1H, m), 8.11-8.13 (1H, m), 7.54-7.60 (2H, m), 7.61 (1H, s), 7.14-7.18 (2H, m), 7.01-7.08 (2H, m), 6.86-6.98 (3H, m), 4.14 (3H, s), 4.08 (3H, s), 4.11-4.20 (2H, m), 4.34-4.44 (2H, m), 2.12-2.24 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 143 3-(2-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (72 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (100 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-fluorophenoxy)-1-propanol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (78 mg, yield 63%).

¹H-NMR (CDCl₃, 400 MHz): 8.41-8.46 (1H, m), 8.13-8.14 (1H, d, J=3.9 Hz), 7.72 (1H, s like), 7.64 (1H, s) 5.94-7.09 (3H, m), 6.87-6.93 (1H, m), 6.53 (1H, d, J=6.6 Hz) 6.47 (1H, s), 4.42 (1H, J=6.2 Hz), 4.35 (1H, t, J=6.2 Hz), 4.15-4.20 (2H, m), 4.15 (3H, s), 4.09 (3H, s), 2.25 (3H, s), 2.08 (3H, s), 2.14-2.25 (2H, m)

Mass spectrometry value (ESI-MS, m/z) 522 (M⁺+1)

Example 144 3-(2-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (71 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (100 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-fluorophenoxy)-1-propanol (61 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (53 mg, yield 42%).

¹H-NMR (CDCl₃, 400 MHz): 8.45-8.49 (1H, m), 8.13 (1H, d like), 7.87 (1H, s), 7.62 (1H, s), 6.87-7.09 (4H, m), 6.56 (1H, d, J=6.3 Hz), 6.45 (1H, s), 4.42 (4H, d, J=6.2 Hz), 4.36 (1H, d, J=6.2 Hz), 4.13-4.20 (2H, m), 4.15 (3H, s), 4.08 (3H, s), 2.05-2.24 (2H, m), 2.26 (3H, s), 2.10 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 522 (M⁺+1)

Example 145 3-(2-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (65 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (90 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-fluorophenoxy)-1-propanol (51 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (52 mg, yield 46%).

¹H-NMR (CDCl₃, 400 MHz): 8.74 (1H, s), 7.96 (1H, s), 7.58 (1H, s), 7.52-7.56 (1H, m), 7.16-7.21 (2H, m), 6.77-7.08 (5H, m), 4.40 (1H, t, J=6.2 Hz), 4.34 (1H, t, J=6.2 Hz), 4.07-4.19 (2H, m), 4.14 (3H, s), 4.09 (3H, s), 2.03-2.27 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 146 3-(2-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2,3-dimethylaniline (65 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (90 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-fluorophenoxy)-1-propanol (51 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (52 mg, yield 46%).

¹H-NMR (CDCl₃, 400 MHz): 8.69 (1H, s like), 8.07 (1H, s), 7.65 (1H, bs), 7.57 (1H, s), 6.80-6.87 (1H, m), 6.89-7.04 (4H, m), 4.35 (1H, t, J=6.2 Hz), 4.28 (1H, d, J=6.2 Hz), 4.08-4.14 (2H, m), 4.12 (3H, s), 4.06 (3H, s), 2.05-2.19 (2H, m), 2.00 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 147 3-(3-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (71 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (108 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. subsequently, 3-(3-fluorophenoxy)-1-propanol (61 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 69%).

¹H-NMR (CDCl₃, 400 MHz): 8.44-8.48 (1H, m), 8.12 (1H, d, J=3.7 Hz), 7.61 (1H, s), 7.57-7.61 (2H, m), 7.14-7.21 (3H, m), 6.92 (1H, d, J=9.2 Hz), 6.57-6.68 (3H, m), 4.39: (1H, t, J=6.2 Hz), 4.35 (1H, d, J=6.2 Hz), 4.12 (3H, s), 4.08 (3H, s), 4.05-4.09 (2H, m), 2.12-2.1 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 148 3-(3-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (66 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (92 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(3-fluorophenoxy)-1-propanol (52 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (63 mg, yield 55%).

¹H-NMR (CDCl₃, 400 MHz): 8.41-8.45 (1H, m), 8.14 (1H, d, J=3.9 Hz), 7.72 (1H, bs), 7.64 (1H, s), 7.16-7.22 (1H, m), 7.00 (1H, dd, J=8.8 Hz, J=5.6 Hz), 6.58-6.70 (2H, m), 6.53 (1H, d, J=6.6 Hz), 6.43-6.49 (1H, m), 4.39 (1H, t, J=6.2 Hz), 4.35 (1H, t, J=6.2 Hz), 4.15 (3H, s), 4.10 (3H, s), 4.05-4.10 (2H, m), 2.25 (3H, d, J=4.9. Hz), 2.08 (3H, s, J=3.2 Hz), 2.13-2.21 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 522 (M⁺+1)

Example 149 3-(3-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (79 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (110 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(3-fluorophenoxy)-1-propanol (62 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (74 mg, yield 54%).

¹H-NMR (CDCl₃, 400 MHz): 8.45-8.50 (1H, m), 8.12 (1H, d, J=3.7 Hz), 7.86 (1H, bs), 7.62 (1H, s), 7.16-7.25 (1H, m), 6.93 (1H, d, J=3.2 Hz), 6.54-6.70 (3H, m), 6.43-6.47 (1H, m), 4.39 (1H, t, J=6.2 Hz), 4.36 (1H, t, J=6.2 Hz), 4.14 (3H, s), 4.08 (3H, s), 4.05-4.10 (2H, m), 2.26 (3H, d, J=4.6 Hz), 2.10 (3H, d, J=5.4H), 2.13-2.22 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 522 (M⁺+1)

Example 150 3-(3-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (82 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (124 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min.

Subsequently, 3-(3-fluorophenoxy)-1-propanol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (59 mg, yield 46%).

¹H-NMR (CDCl₃, 400 MHz): 8.69 (1H, s), 8.01 (1H, s), 7.54 (1H, s), 7.46-7.54 (2H, m), 7.10-7.15 (3H, m), 6.76-6.85 (1H, m), 6.51-6.64 (2H, m), 4.32 (1H, t, J=6.2 Hz), 4.29 (1H, t, J=6.2 Hz), 4.10 (3H, s), 4.04 (3H, s), 3.96-4.04 (2H, m), 2.05-2.15 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 151 3-(3-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2,3-dimethylaniline (68 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (94 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(3-fluorophenoxy)-1-propanol (53 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 56%).

¹H-NMR (CDCl₃, 400 MHz): 8.74 (1H, s), 8.08 (1H, s), 7.67 (1H, bs), 7.61 (1H, s), 7.14-7.23 (1H, m), 6.96-7.02 (1H, m), 6.55-6.68 (2H, m), 6.43-6.53 (1H, m), 4.30-4.38 (2H, m), 4.16 (3H, s), 4.10 (3H, s), 4.03-4.10 (2H, m), 2.22-2.25 (3H, m), 2.10-2.18 (2H, m), 2.04-2.07 (3H, m)

Mass spectrometry value (ESI-MS, m/z) 523 (M⁺+1)

Example 152 3-(4-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (71 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (108 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-fluorophenoxy)-1-propanol (61 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (81 mg, yield 64%).

¹H-NMR (CDCl₃, 400 MHz): 8.45 (1H, d, J=4.2 Hz), 8.12 (1H, d, J=3.6 Hz), 7.62 (1H, s), 7.56-7.62 (2H, m), 7.14-7.18 (2H, m), 6.94-6.98 (1H, m), 6.80-6.89 (2H, m), 6.67 (1H, d, J=6.4 Hz), 4.39 (1H, t, J=6.2 Hz), 4.36 (1H, t, J=6.2 Hz), 4.14 (3H, s), 4.08 (3H, s), 4.04 (2H, t, J=6.0 Hz), 2.12-2.20 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 153 3-(4-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (66 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (92 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-fluorophenoxy)-1-propanol (52 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (79 mg, yield 70%).

¹H-NMR (CDCl₃, 400 MHz): 8.44 (1H, dd, J=6.2 Hz), 8.13 (1H, d, J=3.9 Hz), 7.72 (1H, bs), 7.64 (1H, s), 6.92-7.02 (3H, m), 6.81-6.85 (1H, m), 6.53 (1H, d, J 35=6.2 Hz), 6.48 (1H, d, J=5.6 Hz), 4.39 (1H, t, J=6.3 Hz), 4.35 (1H, t, J=6.3 Hz), 4.15 (3H, s), 4.09 (3H, s), 4.04 (2H, t, J=6.1 Hz), 2.25 (3H, d, J=6.3 Hz), 2.08 (3H, d, J=3.2 Hz), 2.13-2.20 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 522 (M⁺+1)

Example 154 3-(4-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (68 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (94 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-fluorophenoxy)-1-propanol (54 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 58%).

¹H-NMR (CDCl₃, 400 MHz): 8.49 (1H, dd, J=6.5 Hz), 8.10 (1H, s), 7.85 (1H, bs), 7.61 (1H, s), 6.78-6.97 (4H, m), 6.56 (1H, d, J=6.3 Hz), 6.50 (1H, d, J=6.8 Hz), 4.38 (1H, t, J=6.3 Hz), 4.34 (1H, t, J=6.3 Hz), 4.13 (3H, s), 4.13 (3H, s), 4.07 (3H, s), 4.04 (2H, t, J=6.0 Hz), 2.25 (3H, d, J=5.6 Hz), 2.09 (3H, d, J=5.1 Hz)

Mass spectrometry value (ESI-MS, m/z): 522 (M⁺+1)

Example 155 3-(4-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (59 mg) was added to toluene/triethylamine=10/1 (6 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (89 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-fluorophenoxy)-1-propanol (51 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (51 mg, yield 49%).

¹H-NMR (CDCl₃, 400 MHz): 8.73 (1H, s), 7.97 (1H, s), 7.58 (1H, s), 7.53-7.57 (2H, m), 7.16-7.19 (2H, m), 6.89-6.98 (2H, m), 6.78-6.85 (2H, m), 4.37 (1H, t, J=6.3 Hz), 4.34 (1H, t, J=6.3 Hz), 4.14 (−3H, s), 4.09 (3H, s), 4.03 (2H, t, J=6.3 Hz), 2.08-2.20 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 156 3-(4-Fluorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2,3-dimethylaniline (68 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (94 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-fluorophenoxy)-1-propanol (53 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 41%).

¹H-NMR (CDCl₃, 400 MHz): 8.71 (1H, s), 7.91 (1H, s), 7.66 (1H, bs), 7.61 (1H, s), 6.91-7.02 (3H, m), 6.78-6.84 (2H, m), 6.44 (1H, bs), 4.37 (1H, t, J=6.5 Hz), 4.33 (1H, t, J=6.5 Hz), 4.14 (3H, s), 4.10 (3H, s), 4.00-4.08 (2H, m), 2.23 (3H, d, J=6.1 Hz), 2.06 (3H, d, J=3.2 Hz), 2.10-2.20 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 157 3-(2-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (72 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (109 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-methoxyphenoxy)-1-propanol (66 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (91 mg, yield 69%).

¹H-NMR (CDCl₃, 400 MHz): 8.47 (1H, bs), 8.12 (1H, s), 7.61 (1H, s), 7.55-7.60 (2H, m), 7.13-7.18 (2H, m), 6.85-6.95 (4H, m), 6.68 (1H, bs), 4.42 (2H, t, J=6.2 Hz), 4.12-4.20 (2H, m), 4.14 (3H, s), 4.08 (3H, s), 3.85 (3H, s), 2.17-2.26 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 158 3-(2-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (70 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (97 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-methoxyphenoxy)-1-propanol (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 63%).

¹H-NMR (CDCl₃, 400 MHz): 8.43 (1H, dd, J=6.6 Hz), 8.14 (1H, d like, J=4.1 Hz), 7.72 (1H, bs), 7.64 (1H, s), 6.99 (1H, d, J=8.8 Hz), 6.86-6.96 (4H, m), 6.53 (1H, d, J=6.6 Hz), 6.47 (1H, bs), 4.41 (2H, t, J=6.3 Hz), 4.15 (3H, s), 4.15 (2H, t, J=6.2 Hz), 4.09 (3H, s), 3.85 (3H, s), 2.24 (3H, s), 2.07 (3H, s), 2.19-2.26 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 159 3-(2-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (68 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (94 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-methoxyphenoxy)-1-propanol (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 51%).

¹H-NMR (CDCl₃, 400 MHz): 8.44 (1H, d, J=6.4 Hz), 8.14 (1H, d like, J=3.9 Hz), 7.87 (1H, bs), 6.87-6.97 (5H, m), 7.62 (1H, s), 6.56 (1H, d, J=6.4 Hz), 6.43 (1H, bs), 4.42 (2H, t, J=6.2 Hz), 4.15 (3H, s), 4.15 (2H, t, J=6.2 Hz), 4.08 (3H, s), 3.85 (3H, s), 2.23 (2H, t, J=6.2 Hz), 2.26 (3H, s), 2.10 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 160 3-(2-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (75 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (114 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-methoxyphenoxy)-1-propanol (69 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (51 mg, yield 35%).

¹H-NMR (CDCl₃, 400 MHz): 8.71 (1H, s), 8.04 (1H, s), 7.54 (1H, s), 7.46-7.53 (2H, m), 6.70-7.20 (7H, m), 4.36 (1H, t, J=6.2 Hz), 4.30 (1H, t, J=6.2 Hz), 4.12 (3H, s), 4.05 (3H, s), 4.05-4.11 (2H, m), 3.79 (3H, s), 2.10-2.20 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 507 (M⁺+1)

Example 161 3-(3-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (70 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (106 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(3-methoxyphenoxy)-1-propanol (64 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (69 mg, yield 54%).

¹H-NMR (CDCl₃, 400 MHz): 8.45 (1H, dd, J=6.3 Hz), 8.13 (1H, d like, J=3.9 Hz), 7.62 (1H, s), 7.55-7.65 (3H, m), 7.12-7.18 (3H, m), 6.65-6.75 (1H, m), 6.43-6.52 (1H, m), 6.44-6.47 (1H, m), 4.22-4.41 (2H, m), 4.14 (3H, s), 4.08 (3H, s), 4.05-4.14 (2H, m), 3.76 (3H, s), 2.14-2.20 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 162 3-(3-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (72 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (100 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(3-methoxyphenoxy)-1-propanol (61 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (83 mg, yield 66%).

¹H-NMR (CDCl₃, 400 MHz): 8.39 (1H, d like, J=6.7 Hz), 8.08 (1H, d like, J=3.4 Hz), 7.60-7.70 (1H, m), 7.59 (1H, s), 7.11 (1H, dd, J=8.2 Hz), 6.94 (1H, d, J=9.0 Hz), 6.39-6.50 (4H, m), 4.34 (2H, t, J=6.3 Hz), 4.09 (3H, s), 4.04 (3H, s), 4.01 (2H, t, J=6.2 Hz), 3.72 (3H, s), 2.19 (3H, s), 2.08-2.15 (2H, m), 2.02 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 163 3-(3-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (73 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (101 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(3-methoxyphenoxy)-1-propanol (62 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (59 mg, yield 46%).

¹H-NMR (CDCl₃, 400 MHz): 8.45-8.55 (1H, m), 8.11 (1H, s), 7.86 (1H, s), 7.62 (1H, s), 7.16 (1H, dd, J=8.2 Hz), 6.92 (1H, s), 6.56 (1H, d, J=6.4 Hz), 6.40-6.52 (4H, m), 4.39 (2H, t, J=6.2 Hz), 4.14 (3H, s), 4.08 (3H, s), 4.07 (2H, t, J=6.4 Hz), 3.77 (3H, s), 2.26 (3H, s), 2.14-2.22 (2H, m), 2.10 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 164 3-(3-Methoxyphenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (75 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (114 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(3-methoxyphenoxy)-1-propanol (69 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (51 mg, yield 35%).

¹H-NMR (CDCl₃, 400 MHz): 8.71 (1H, s), 8.04 (1H, s), 7.54 (1H, s), 7.46-7.53 (2H, m), 6.70-7.20 (7H, m), 4.36 (1H, t, J=6.2 Hz), 4.30 (1H, t, J=6.2 Hz), 4.12 (3H, s), 4.05 (3H, s), 4.05-4.11 (2H, m), 3.79 (3H, s), 2.10-2.20 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 507 (M⁺+1)

Example 165 2-[(2,5-dimethylphenyl)sulfanyl]ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (77 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (105 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-[(2,5-dimethylphenyl)sulfanyl]-1-ethanol (78 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (105 mg, yield 74%).

¹H-NMR (CDCl₃, 400 MHz): 8.43-8.48 (1H, m), 8.13 (1H, d like, J=3.9 Hz), 7.62 (1H, s), 7.56 (2H, d, J=9.0 Hz), 7.16 (2H, d, J=9.0 Hz), 7.02 (2H, d, J=9.0 Hz), 6.84 (1H, s), 6.76 (1H, s), 6.67 (1H, d, J=6.6 Hz), 4.35 (2H, t, J=6.6 Hz), 4.15 (3H, s), 4.08 (3H, s), 3.18 (2H, t, J=6.6 Hz), 2.27 (6H, s)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 166 2-[(2,5-Dimethylphenyl)sulfanyl]ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (62 mg) was added to toluene/triethylamine=10/1 (61 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (85 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 ml. Subsequently, 2-[(2,5-dimethylphenyl)sulfanyl]-1-ethanol (55 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 81%).

¹H-NMR (CDCl₃, 400 MHz): 8.44 (1H, d, J=6.6 Hz), 8.14 (1H, s, J=4.2 Hz), 7.72 (1H, bs), 7.64 (1H, s), 7.01-7.04 (2H, m), 6.99 (1H, s), 6.84 (1H, s), δ 53 (1H, d, J=6.4 Hz), 6.43 (1H, s), 3.71 (1H, t, J=6.0 Hz), 4.15 (3H, s), 4.09 (3H, s), 3.19 (2H, t, J=6.0 Hz), 2.27 (6H, s), 2.23 (3H, s), 2.08 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 167 2-[(2,5-Dimethylphenyl)sulfanyl]ethyl N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (68 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (97 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-[(2,5-dimethylphenyl)sulfanyl]-1-ethanol (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (79 mg, yield 66%).

¹H-NMR (CDCl₃, 400 MHz): 8.45 (1H, dd, J=6.6 Hz), 8.13 (1H, d, J=4.2 Hz), 7.86 (1H, s), 7.62 (1H, s), 7.02 (2H, s), 6.93 (1H, s), 6.84 (1H, s), 6.55 (1H, d, J=6.6 Hz), 6.40 (1H, s), 4.36 (1H, t, J=6.7 Hz), 4.15 (3H, s), 4.08 (3H, s), 3.20 (2H, t, J=6.7 Hz), 2.27 (6H, s), 2.24 (3H, s), 2.11 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 168 2-[(2,5-Dimethylphenyl)sulfanyl]ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (70 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (108 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-[(2,5-dimethylphenyl)sulfanyl]-1-ethanol (65 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (101 mg, yield 79%).

¹H-NMR (CDCl₃, 400 MHz): 8.77 (1H, s), 8.09 (1H, S), 7.59 (1H, s), 7.53 (2H, d, J=9.0 Hz), 7.17 (2H, d, J=8.8 Hz), 6.97-7.03 (2H, m), 6.72-6.85 (2H, m), 4.34 (2H, t, J=6.6 Hz), 4.16 (3H, s), 4.10 (3H, s), 3.17 (2H, t, J=6.6 Hz), 2.27 (6H, s)

Mass spectrometry value (ESI-MS, m/z): 507 (M⁺+1)

Example 169 3-[(2,5-Dimethylphenyl)sulfanyl)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (70 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (105 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-[(2,5-dimethylphenyl)sulfanyl]-1-propanol (78 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 37%).

¹H-NMR (CDCl₃, 400 MHz): 8.45 (1H, dd, J=6.6 Hz), 8.12 (1H, s), 7.62 (1H, s), 7.56-7.61 (2H, m), 7.15-7.61 (2H, m), 7.15-7.25 (3H, m), 6.96 (1H, s), 6.80-6.85 (1H, m), 6.67 (1H, d, J=6.4 Hz), 4.36 (1H, t, J=6.4 Hz), 4.31 (1H, t, J=6.4 Hz), 4.14 (3H, s), 4.08 (3H, s), 3.00 (2H, t, J=7.1 Hz), 2.27 (6H, s), 1.97-2.25 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 520 (M⁺+1)

Example 170 3-[(2,5-Dimethylphenyl)sulfanyl]propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (72 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (100 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-[(2,5-dimethylphenyl sulfanyl]-1-propanol (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (33 mg, yield 25%).

¹H-NMR (CDCl₃, 400 MHz): 8.4.0-8.46 (1H, m), 8.14 (1H, s), 7.73 (1H, bs), 7.65 (1H, s), 6.94-7.02 (3H, m), 6.82-7.02 (3H, m), 6.82 (1H, s), 6.53 (1H, d, J=6.6 Hz), 6.43-6.48 (1H, m), 4.28-4.37 (2H, m), 4.15 (3H, s), 4.09 (3H, s), 4.00 (2H, t, J=7.1 Hz), 2.27 (6H, s), 2.25 (3H, s), 2.08 (3H, s), 1.98-2.20 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 548 (M⁺+1)

Example 171 3-[(2,5-Dimethylphenyl)sulfanyl]propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (68 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (97 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-[(2,5-dimethylphenyl)sulfanyl]-1-propanol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (51 mg, yield 42%).

¹H-NMR (CDCl₃, 400 MHz): 8.41-8.45 (1H, m), δ 14 (1H, bs), 7.68 (1H, bs), 7.62 (1H, s), 6.97 (1H, s), 6.92-6.96 (1H, m), 6.82 (1H, s), 6.56 (1H, d, J=6.6 Hz), 6.40-6.45 (1H, m), 4.36 (1H, t, J=6.0 Hz), 4.32 (1H, t, J=6.0 Hz), 3.00 (2H, t, J=7.1 Hz), 2.27 (6H, s), 2.26 (3H, s), 2.14-2.20 (1H, m), 2.11 (3H, s), 1.98-2.05 (1H, m)

Mass spectrometry value (ESI-MS, m/z): 548 (M⁺+1)

Example 172 3-[(2,5-Dimethylphenyl)sulfanyl]propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (66 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (1001 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-[(2,5-dimethylphenyl)sulfanyl]-1-propanol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (29 mg, yield 23%).

¹H-NMR (CDCl₃, 400 MHz): 8.75 (1H, s), 8.07 (1H, s), 7.59 (1H, s), 7.52-7.58 (2H, m), 6.79-7.21 (5H, m), 4.34 (1H, d, J=6.1 Hz), 4.30 (1H, d, J=6.1 Hz), 4.16 (3H, s), 4.10 (3H, s), 2.99 (2H, t, J=7.1 Hz), 2.27 (6H, s), 2.11-2.19 (1H, m), 2.15-2.03 (1H, m)

Mass spectrometry value (ESI-MS, m/z): 521 (M⁺+1)

Example 173 3-(2-Pyridylsulfanyl)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (111 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-pyridylsulfanyl)-1-propanol (63 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (18 mg, yield 13%).

¹H-NMR (CDCl₃, 400 MHz): 8.39-8.44 (2H, m), 7.90-7.95 (1H, m), 7.64-7.70 (1H, m), 7.63 (1H, s), 7.44-7.50 (1H, m), 7.15-7.20 (1H, m), 6.95-7.02 (2H, m), 6.42-6.48 (1H, m), 4.33 (2H, t, J=6.2 Hz), 4.12 (3H, s), 4.08 (3H, s), 3.29 (2H, t, J=7.1 Hz), 2.25 (3H, s), 2.09-2.15 (2H, m), 2.09 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 521 (M⁺+1)

Example 174 3-(2-Pyridylsulfanyl)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (78 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (110 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-pyridylsulfanyl)-1-propanol (62 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (13 mg, yield 10%).

¹H-NMR (CDCl₃, 400 MHz): 8.75-8.79 (1H, m), 8.41-8.47 (1H, m), 8.12 (1H, s), 8.06-8.14 (1H, m), 7.99 (1H, bs), 7.81 (1H, s), 7.69 (1H, d, J=8.5 Hz), 7.63 (1H, s like), 7.52-7.58 (1H, m), 6.92 (1H, s), 6.58 (1H, d, J=6.3 Hz), 4.30 (2H, t, J=5.6 Hz), 4.14 (3H, s), 4.09 (3H, s), 3.99 (2H, t, J=7.3 Hz), 2.40 (3H, s), 2.08-2.22 (2H, m), 2.08 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 521 (M⁺+1)

Example 175 3-(2-Pyridylsulfanyl)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (73 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (110 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-pyridylsulfanyl)-1-propanol (62 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (5 mg, yield 4%).

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 176 4-Chloro-2-methylphenyl {4-[(6,7-dimethoxy-4-quinolyl)oxy]anilino}methanethioate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (88 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (70 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-methyl-4-chlorothiophenol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (108 mg, yield 70%).

Mass spectrometry value (ESI-MS, m/z): 482 (M⁺+1)

Example 177 4-Chloro-2-methylphenyl {4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylanilino}methanethioate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (82 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (114 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-methyl-4-chlorothiophenol (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (91 mg, yield 66%).

Mass spectrometry value (ESI-MS, m/z): 510 (M⁺+1)

Example 178 4-Chloro-2-methylphenyl {4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylanilino}methanethioate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (79 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (110 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-methyl-4-chlorothiophenol (58 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (71 mg, yield 53%).

Mass spectrometry value (ESI-MS, m/z): 510 (M⁺+1)

Example 179 4-Chloro-2-methylphenyl {4-[(6,7-dimethoxy-4-quinazolinyl)oxy]anilino}methanethioate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (121 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-methyl-4-chlorothiophenol (64 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 49%).

Mass spectrometry value (ESI-MS, m/z): 493 (M⁺+1)

Example 180 1-[3-(Trifluoromethoxy)phenyl]ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (82 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (124 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-trifluoromethoxy-α-methylbenzyl alcohol (85 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 39%).

¹H-NMR (CDCl₃, 400 MHz): 8.39 (1H, dd, J=6.6 Hz), 8.07 (1H, s like), 7.50-7.56 (2H, m), 7.31-7.36 (3H, m), 7.23-7.28 (1H, m), 7.08-7.13 (2H, m), 6.82 (1H, s), 6.60 (1H, d, J=6.6 Hz), 5.85 (1H, q, J=6.6 Hz), 4.09 (3H, s), 4.02 (3H, s), 1.55 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺¹+1)

Example 181 1-[3-(Trifluoromethoxy)phenyl]ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (88 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (122 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-trifluoromethoxy-α-methylbenzyl alcohol (83 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (73 mg, yield 46%).

¹H-NMR (CDCl₃, 400 MHz): 8.42 (1H, dd, J=6.5 Hz), 8.13 (1H, s), 7.63-7.75 (2H, m), 6.96-7.42 (5H, m), 6.51 (2H, d, J=6.5 Hz), 5.89 (1H, q, J=6.6 Hz), 4.15 (3H, s), 4.09 (3H, s), 2.24 (3H, s), 2.07 (3H, s), 1.61 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 558 (M⁺+1)

Example 182 1-[3-(Trifluoromethoxy)phenyl]ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (125 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-trifluoromethoxy-α-methylbenzyl alcohol (85 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (78 mg, yield 48%).

¹H-NMR (CDCl₃, 400 MHz): 8.43 (1H, dd, J=6.6 Hz), 8.13 (1H, s), 7.85 (1H, s), 7.62 (1H, s), 7.40 (1H, dd, J=7.8 Hz), 7.31 (1H, d, J=7.8 Hz), 7.16 (1H, d, J=8.0 Hz), 6.93 (1H, s), 6.54 (1H, d, J=6.6 Hz), 6.48 (1H, s), 5.89 (1H, q, J=6.7 Hz), 4.15 (3H, s), 4.08 (3H, s), 2.27 (3H, s), 2.09 (3H, s), 1.62 (3H, d, J=6.7 Hz)

Mass spectrometry value (ESI-MS, m/z): 558 (M⁺+1)

Example 183 1-[3-(Trifluoromethoxy)phenyl]ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (82 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (124 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-trifluoromethoxy-α-methylbenzyl alcohol (85 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 31%).

¹H-NMR (CDCl₃, 400 MHz): 8.75 (1H, s), 8.11 (1H, s), 7.53-7.59 (3H, m), 7.38 (1H, dd, J=7.9 Hz), 7.30 (1H, d, J=7.9 Hz), 7.12-7.19 (3H, m), 6.87 (1H, s), 5.89 (1H, q, J=6.6 Hz), 4.16 (3H, s), 4.10 (3H, s), 1.60 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 530 (M⁺+1)

Example 184 1-Phenylbutyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (78 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (118 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 1-phenyl-1-butanol (59 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (78 mg, yield 58%).

¹H-NMR (CDCl₃, 400 MHz): 8.43 (1H, dd, J=6.6 Hz), 8.12 (1H, s like), 7.60 (1H, s), 7.53-7.58 (2H, m), 7.23-7.38 (4H, m), 7.12-7.15 (2H, m), 6.80 (1H, s), 6.64 (1H, d, J=6.6 Hz), 5.72-5.78 (1H, m), 4.14 (3H, s), 4.07 (3H, s), 1.75-2.03 (2H, m), 1.35-1.45 (2H, m), 0.94 (2H, d, J=7.3 Hz)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺¹+1)

Example 185 1-Phenylbutyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (125 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 1-phenyl-1-butanol (62 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (59 mg, yield 40%).

¹H-NMR (CDCl₃₁ 400 MHz): 8.36 (1H, dd, J=6.5 Hz), 8.08 (1H, s), 7.67 (1H, d, J=8.8 Hz), 7.59 (1H, s) 7.24-7.34 (5H, m), 6.92 (1H, d, J=8.8 Hz), 6.42-6.47 (2H, m), 5.69 (1H, t, J=6.9 Hz), 4.10 (3H, s) 4.04 (3H, s), 2.18 (3H, s), 2.01 (3H, s), 1.70-2.00 (2H, m), 1.2-1.42 (2H, m), 0.90 (3H, t, J=7.4 Hz)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 186 1-Phenylbutyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (89 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (126 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 1-phenyl-1-butanol (63 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (58 mg, yield 39%).

¹H-NMR (CDCl₃, 400 MHz): 8.43 (1H, dd, J=6.5 Hz), 8.12 (1H, s like), 7.89 (1H, s), 7.61 (1H, s), 7.26-7.40 (5H, m), 6.91 (1H, s), 6.53 (1H, d, J=6.5 Hz), 6.47 (1H, s), 5.71-5.76 (1H, m), 4.14 (3H, s), 4.08 (3H, s9, 2.25 (3H, s), 2.07 (3H, s), 1.75-2.05 (2H, m), 1.25-1.50 (2H, m), 0.95 (3H, t, J=7.3 Hz)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 187 1-Phenylbutyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (76 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (115 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 1-phenyl-1-butanol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (38 mg, yield 29%).

¹H-NMR (CDCl₃, 400 MHz): 8.71 (1H, s), 8.07 (1H, s), 7.54 (1H, s), 7.44-7.52 (2H, m), 7.18-7.33 (5H, m), 7.08-7.13 (2H, m), 6.73 (1H, s), 5.65-5.72 (1H, m), 4.12 (3H, s), 4.05 (3H, s), 1.65-1.95 (2H, m), 1.30-1.40 (2H, m), 0.89 (3H, t, J=7.4 Hz)

Mass spectrometry value (ESI-MS, m/z): 475 (M⁺+1)

Example 188 2-(Dimethylamino)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (83 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (40 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-dimethylaminoethanol (40 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (31 mg, yield 25%).

¹H-NMR (CDCl₃, 400 MHz): 8.41 (1H, d, J=5.4 Hz), 7.56-7.65 (2H, m), 7.43 (1H, s), 7.20-7.26 (2H, m), 6.97 (1H, d, J=8.8 Hz), 6.25 (1H, d, J=5.1 Hz), 4.34-4.41 (2H, m), 4.05 (2H, s), 4.04 (3H, s), 2.92 (2H, bs), 2.57 (6H, bs)

Mass spectrometry value (ESI-MS, m/z): 412 (M⁺¹+1)

Example 189 2-(Dimethylamino)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (111 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-dimethylaminoethanol (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (41 mg, yield 35%).

¹H-NMR (CDCl₃, 400 MHz): 8.41 (1H, d, =5.3 Hz), 7.59 (2H, s), 7.42 (1H, s), 6.96 (1H, d, H=8.8 Hz), 6.24 (1H, d, J=5.3 Hz), 4.30-4.38 (2H, m), 4.94 (3H, s), 4.03 (3H, s), 2.81 (2H, bs), 2.47 (6H, bs), 2.25 (3H, s), 2.09 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 441 (M⁺+1)

Example 190 2-(Dimethylamino)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (85 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (115 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-dimethylaminoethanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (28 mg, yield 22%).

¹H-NMR (CDCl₃, 400 MHz):

Mass spectrometry value (ESI-MS, m/z): 441 (M⁺+1)

Example 191 2-(Dimethylamino)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (74 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (112 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-dimethylaminoethanol (32 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (13 mg, yield 12%).

¹H-NMR (CDCl₃, 400 MHz): 8.42 (1H, m), 8.07 (1H, s) 7.10-7.70 (5H, m), 6.62-6.68 (1H, m), 4.47-4.52 (2H, m), 4.14 (3H, s), 4.08 (3H, s), 3.30-3.35 (2H, m), 2.94 (6H, s)

Mass spectrometry value (ESI-MS, m/z): 413 (M⁺+1)

Example 192 4-(Dimethylamino)butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (130 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-dimethylaminopropanol (40 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (22 mg, yield 17%).

Example 193 4-(Dimethylamino)butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (76 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (106 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-dimethylaminopropanol (40 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (29 mg, yield 25%).

Mass spectrometry value (ESI-MS, m/z): 469 (M⁺+1)

Example 194 4-(Dimethylamino)butyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (75 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (114 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-dimethylaminopropanol (43 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (18 mg, yield 15%).

Mass spectrometry value (ESI-MS, m/z): 413 (M⁺+1)

Example 195 2-Methyl-1-phenylpropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (77 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (118 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-methyl-1-phenyl-1-propanol (39 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (78 mg, yield 59%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.45 (1H, m), 8.10-8.13 (1H, m), 7.10-7.61 (10H, m), 6.62-6.65 (1H, m), 5.45 (1H, d, J=7.8 Hz), 4.14 (3H, s), 4.07 (3H, s), 2.00-2.25 (1H, m), 1.04 (3H, d, J=6.6 Hz), 0.83 (3H, d, J=6.8 Hz).

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺¹+1)

Example 196 2-Methyl-1-phenylpropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (111 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-methyl-1-phenyl-1-propanol (55 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (69 mg, yield 52%).

¹H-NMR (CDCl₃, 400 MHz): 8.38-8.43 (1H, m), 8.11-8.15 (1H, m), 7.00-7.80 (8H, m), 6.95-7.00 (1H, m), 6.47-6.52 (1H, m), 5.45 (1H, d, J=7.6 Hz), 4.14 (3H, s), 4.09 (3H, s), 2.23 (3H, s), 2.06 (3H, s), 2.00-2.25 (1H, m), 1.04 (3H, d, J=6.6 Hz), 0.83 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 197 2-Methyl-1-phenylpropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (124 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-methyl-1-phenyl-1-propanol (61 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (58 mg, yield 44%).

¹H-NMR (CDCl₃, 400 MHz): 8.39-8.44 (1H, m), 8.12-8.14 (1H, m), 7.85-7.90 (1H, s like), 7.61 (1H, s), 7.24-7.36 (5H, m), 6.91 (1H, s), 6.45-6.55 (2H, m), 5.45 (1H, d, J=7.8 Hz), 4.14 (3H, s), 4.08 (3H, s), 2.26 (3H, s), 2.10-2.22 (1H, m), 2.07 (3H, s), 1.05 (3H, d, J=6.6 Hz), 0.83 (3H, d, J=6.8 Hz)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 198 2-Methyl-1-phenylpropyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (75 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (137 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-methyl-1-phenyl-1-propanol (56 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (38 mg, yield 29%).

¹H-NMR (CDCl₃, 400 MHz): 8.72 (1H, s), 8.09 (1H, s), 7.58 (1H, s), 7.55 (2H, d, J=8.8 Hz), 7.20-7.36 (5H, m), 7.13-7.16 (2H, m), 6.93 (1H, bs), 5.45 (1H, d, J=7.6 Hz), 4.15 (3H, s), 4.09 (3H, s), 2.09-2.18 (1H, m), 1.02 (3H, d, J=6.6 Hz), 0.82 (3H, d, J=6.8 Hz)

Mass spectrometry value (ESI-MS, m/z): 475 (M⁺+1)

Example 199 1-[3-(Dimethylamino)phenyl]ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (78 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-dimethylamino-α-methylbenzyl alcohol (65 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 44%).

¹H-NMR (CDCl₃, 400 MHz): 8.39 (1H, d, J=5.6 Hz), 7.42-7.57 (3H, m), 7.06-7.22 (2H, m), 6.54-6.74 (5H, m), 6.42 (1H, d, J=5.6 Hz), 5.80 (1H, q, J=6.6 Hz), 4.01 (3H, s), 3.99 (3H, s), 2.90 (3H, s), 2.89 (3H, s), 1.56 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 489 (M⁺¹+1)

Example 200 1-[3-(Dimethylamino)phenyl]ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (83 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-dimethylamino-α-methylbenzyl alcohol (62 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 55%).

¹H-NMR (CDCl₃, 400 MHz): 8.41 (1H, d, J=5.4 Hz), 7.48-7.65 (3H, m), 7.20-7.26 (1H, m), 6.96 (1H, d, J=8.8 Hz), 6.65-6.78 (3H, m), 6.42 (1H, bs), 6.25-6.30 (1H, m), 5.85 (1H, q, J=6.6 Hz), 4.04-4.06 (6H, m), 2.95 (6H, s), 2.22 (3H, s), 2.08 (3H, s), 1.61 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z): 517 (M⁺+1)

Example 201 1-[3-(Dimethylamino)phenyl]ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (110 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-dimethylamino-α-methylbenzyl alcohol (60 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (58 mg, yield 43%).

¹H-NMR (CDCl₃, 400 MHz): 8.41 (1H, d, J=5.6 Hz), 7.80 (1H, bs), 7.57 (1H, s), 7.55 (1H, bs), 7.20-7.26 (1H, m), 6.89 (1H, s), 6.72-6.7.9 (2H, m), 6.65-6.70 (1H, m), 6.41 (1H, bs), 6.31 (1H, q, J=5.4 Hz), 5.85 (1H, q, J=6.6 Hz), 4.05 (3H, s), 4.05 (3H, s), 2.96 (6H, s), 2.22 (3H, s), 2.10 (3H, s), 1.62 (3H, d, J=6.6 Hz)

Mass spectrometry value (ESI-MS, m/z) 517 (M⁺+1)

Example 202 1-[3-(Dimethylamino)phenyl]ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-dimethylamino-α-methylbenzyl alcohol (66 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (51 mg, yield 36%).

¹H-NMR (CDCl₃, 400 MHz): 8.54 (1H, s), 7.48 (1H, s), 7.42 (1H, d, J=7.8 Hz), 7.25 (1H, s), 7.10-7.20 (3H, m), 6.58-6.74 (5H, m), 5.80 (1H, q, J=6.5 Hz), 3.99 (3H, s), 3.99 (3H, s), 2.90 (6H, s), 1.55 (3H, d, J=6.5 Hz)

Mass spectrometry value (ESI-MS, m/z): 490 (M⁺+1)

Example 203 2-(2-Fluorophenoxy)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (60 mg) was added to toluene/triethylamine=10/1 (6 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (91 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-(2-fluorophenoxy)-1-ethanol (47 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (52 mg, yield 50%).

¹H-NMR (CDCl₃, 400 MHz): 8.43-8.49 (1H, m), 8.13 (1H, d, J=3.9 Hz), 7.62 (1H, s), 7.59 (2H, d, J=8.6 Hz), 7.17 (2H, d, J=9.0 Hz), 6.90-7.12 (5H, m), 6.68 (1H, d, J=6.1 Hz), 4.54-4.59 (2H, m), 4.28-4.33 (2H, m), 4.15 (3H, s), 4.08 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 479 (M⁺+1)

Example 204 2-(2-Fluorophenoxy)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (62 mg) was added to toluene/triethylamine=10/1 (6 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (86 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-(2-fluorophenoxy)-1-ethanol (45 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (49 mg, yield 47%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.45 (1H, t, J=6.5 Hz), 8.14 (1H, s like), 7.72 (1H, bs), 7.64 (1H, s), 6.90-7.12 (5H, m), 6.59 (1H, bs), 6.53 (1H, d, J=6.4 Hz), 4.56 (2H, t, J=4.6 Hz), 4.30 (2H, t, J=4.6 Hz), 4.15 (3H, s), 4.09 (3H, s), 2.25 (3H, s), 2.08 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 205 2-(2-Fluorophenoxy)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (55 mg) was added to toluene/triethylamine=10/1 (6 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (76 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-(2-fluorophenoxy)-1-ethanol (40 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 66%).

¹H-NMR (CDCl₃, 400 MHz): 8.46-8.53 (1H, m), 8.11 (1H, d, J=1.7 Hz), 7.85 (1H, bs), 7.62 (1H, s), 6.85-7.12 (5H, m), 6.54-6.64 (2H, m), 4.54-4.58 (2H, m), 4.29-4.32 (2H, m), 4.14 (3H, s), 4.08 (3H, s), 2.26 (3H, s), 2.10 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 206 2-(2-Fluorophenoxy)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene/triethylamine=10/1 (5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (76 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-(2-fluorophenoxy)-1-ethanol (40 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (38 mg, yield 44%).

¹H-NMR (CDCl₃, 400 MHz): 8.75 (1H, s), 7.99 (1H, s), 7.59 (1H, s), 7.54 (2H, d, J=8.8 Hz), 7.19 (2H, d, J=9.0 Hz), 6.85-7.12 (5H, m), 4.53-4.56 (2H, m), 4.28-4.32 (2H, m), 4.15 (3H, s), 4.09 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 207 2-(3-Fluorophenoxy)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (62 mg) was added to toluene/triethylamine=10/1 (6 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (92 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-(3-fluorophenoxy)-1-ethanol (48 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (55 mg, yield 51%).

¹H-NMR (CDCl₃, 400 MHz): 8.43-8.49 (1H, m), 8.10-8.13 (1H, m), 7.57-7.64 (3H, m), 6.60-7.25 (7H, m), 4.52-4.57 (2H, m), 4.18-4.27 (2H, m), 4.14 (3H, s), 4.08 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 479 (M⁺+1)

Example 208 2-(3-Fluorophenoxy)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (70 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (97 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-(3-fluorophenoxy)-1-ethanol (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (78 mg, yield 67%).

¹H-NMR (CDCl₃, 400 MHz): 8.42-8.49 (1H, m), 8.12-8.14 (1H, m), 7.73 (1H, bs), 7.64 (1H, s), 7.21 (1H, d, J=8.0 Hz), 7.00 (1H, d, J=8.8 Hz), 6.50-6.74 (4H, m), 4.54 (2H, t, J=4.5 Hz), 4.21 (2H, t, J=4.5 Hz), 4.15 (3H, s), 4.09 (3H, s), 2.25 (3H, s), 2.08 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 209 2-(3-Fluorophenoxy)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (56 mg) was added to toluene/triethylamine=10/1 (6 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (78 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-(3-fluorophenoxy)-1-ethanol (40 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (54 mg, yield 57%).

¹H-NMR (CDCl₃, 400 MHz): 8.40-8.50 (1H, m), 8.11 (1H, s), 8.00 (1H, s), 7.84-7.91 (1H, m), 7.60-7.67 (2H, m), 6.40-6.99 (5H, m), 4.08-4.28 (4H, m), 4.14 (3H, s), 4.09 (3H, s), 2.26 (3H, s), 2.11 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 210 2-(3-Fluorophenoxy)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (55 mg) was added to toluene/triethylamine=10/1 (6 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (83 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 2-(3-fluorophenoxy)-1-ethanol (43 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (28 mg, yield 29%).

¹H-NMR (CDCl₃, 400 MHz): 8.75 (1H, m), 8.05 (1H, s like), 7.59 (1H, s), 7.50-7.58 (2H, m), 7.17-7.24 (2H, m), 6.60-6.73 (4H, m), 4.52-4.56 (2H, m), 4.19-4.23 (2H, m), 4.16 (3H, s), 4.10 (3H, s)

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 211 3-(2-Chlorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2,3-aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (111 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(2-chlorophenoxy)-1-propanol (69 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (70 mg, yield 50%).

¹H-NMR (CDCl₃, 400 MHz): 8.74 (1H, d, J=1.7 Hz), 8.08 (1H, s), 7.70 (1H, bs), 7.62 (1H, s), 7.32-7.36 (1H, m), 7.17-7.22 (1H, m), 7.00 (1H, dd, J=6.8 Hz, J=9.3 Hz), 6.85-6.95 (2H, m), 6.44 (1H, bs), 4.43 (1H, t, J=6.2 Hz), 4.34 (1H, t, J=6.2 Hz), 4.10-4.20 (1H, m), 4.18 (3H, s), 4.11 (3H, s), 3.60-3.70 (1H, m), 2.23 (1H, d, J=5.9 Hz), 2.06 (1H, d, J=4.1 Hz), 2.08-2.22 (2H, m)

Mass spectrometry value (ESI-MS, m/z): 539 (M⁺+1)

Example 212 3-(3-Chlorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2,3-aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (111 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(3-chlorophenoxy)-1-propanol (62 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (65 mg, yield 46%).

¹H-NMR (CDCl₃, 400 MHz): 8.75 (1H, d, J=2.7 Hz), 8.14 (1H, s), 7.70 (1H, bs), 7.62 (1H, s), 7.15-7.22 (1H, m), 6.97-7.03 (1H, m), 6.87-6.95 (1H, m), 6.76-6.82 (1H, m), 6.42 (1H, bs), 4.32-4.39 (2H, m), 4.18 (3H, s), 4.11 (3H, s), 4.03-4.08 (1H, m), 3.62-3.68 (1H, m), 2.23-2.26 (3H, m), 2.12-2.21 (2H, m), 2.05-2.07 (3H, m)

Mass spectrometry value (ESI-MS, m/z): 539 (M⁺+1)

Example 213 3-(4-Chlorophenoxy)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2,3-aniline (82 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (114 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-(4-chlorophenoxy)-1-propanol (71 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (85 mg, yield 59%).

¹H-NMR (CDCl₃, 400 MHz): 8.74 (1H, s like), 8.09 (1H, s), 7.69 (1H, bs), 7.62 (1H, s), 7.19-7.23 (2H, m), 7.97-7.02 (1H, m), 6.79-6.84 (2H, m), 6.42 (1H, bs), 4.32-4.39 (2H, m), 4.17 (3H, s), 4.11 (3H, s), 4.02-4.09 (2H, m), 2.23-2.26 (3H, m), 2.10-2.20 (2H, m), 2.05-2.07 (3H, m)

Mass spectrometry value (ESI-MS, m/z): 539 (M⁺+1)

Example 214 3-Methoxyphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (150 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 10 min. Next, 3-methoxyphenol (55 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (108 mg, yield 68%)

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.29 (s, 3H), 4.07 (s, 3H), 4.09 (s, 3H), 6.54 (brs, 1H), 7.13-7.29 (m, 8H), 7.59-7.60 (m, 3H), 8.49 (d, J=5.9 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 447 (M⁺+1)

Example 215 Propyl N-{4-[(6,7-Dimethoxy-4-quinolin)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (138 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 10 min. Next, 1-propanol (28 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (120 mg, yield 87%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.95 (t, J=7.6 Hz, 3H), 1.63-1.66 (m, 2H), 2.07 (s, 3H), 2.20 (s, 3H), 4.04 (t, J=6.8 Hz, 2H), 4.05 (s, 6H), 6.67 (d, J=6.6 Hz, 1H), 7.15 (d, J=8.3 Hz, 1H), 7.37 (d, J=9.0 Hz, 1H), 7.60 (s, 1H), 7.79 (s, 1H), 8.77 (d, J=6.6 Hz, 1H), 9.06 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 411 (M⁺+1)

Example 216 Phenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 10 min. Next, phenol (48 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (97 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 4.03 (s, 3H), 4.04 (s, 3H), 6.83 (d, J=6.3 Hz, 1H), 7.24-7.30 (m, 3H), 7.38-7.47 (m, 3H), 7.57 (s, 1H), 7.72-7.74 (m, 3H), 8.79 (d, J=6.6 Hz, 1H), 10.50 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 417 (M⁺+1)

Example 217 Phenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (139 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 10 min. Next, phenol (44 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (73 mg, yield 49%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.10 (s, 3H), 2.30 (s, 3H), 4.05 (s, 6H), 6.69 (d, J=6.6 Hz, 1H), 7.15-7.28 (m, 4H), 7.42-7.48 (m, 3H), 7.61 (s, 1H), 7.79 (s, 1H), 8.76 (d, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 218 Benzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, phenylmethanol (51 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (137 mg, yield 89%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13 (s, 3H), 2.27 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.24 (s, 2H), 6.52 (s, 1H), 6.59 (brs, 1H), 6.95 (s, 1H), 7.26-7.45 (m, 5H), 7.64 (s, 1H), 7.93 (s, 1H), 8.14 (s, 1H), 8.51 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 459 (M⁺+1)

Example 219 Benzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, phenylmethanol (51 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (120 mg, yield 78%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 2.26 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.24 (s, 2H), 6.55 (s, 2H), 7.03 (d, J=8.8 Hz, 1H), 7.37-7.43 (m, 5H), 7.67 (s, 1H), 7.76 (brs, 1H), 8.15 (s, 1H), 8.50 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 459 (M⁺+1)

Example 220 Benzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, phenylmethanol (55 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (100 mg, yield 58%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.12 (s, 3H), 4.19 (s, 3H), 5.23 (s, 2H), 6.96 (s, 1H), 7.19 (d, J=9.0 Hz, 2H), 7.35-7.43 (m, 5H), 7.59 (d, J=8.8 Hz, 2H), 7.61 (s, 1H), 8.14 (s, 1H), 8.79 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 432 (M⁺+1)

Example 221 Cyclohexyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclohexanol (47 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 53%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.49-1.57 (m, 10H), 1.76-1.80 (m, 2H), 1.97-2.01 (m, 2H), 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 6.39 (s, 1H), 6.59 (d, J=9.0 Hz, 1H), 6.94 (s, 1H), 7.65 (s, 1H), 7.95 (s, 1H), 8.15 (s, 1H), 8.49 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 451 (M⁺+1)

Example 222 Cyclohexyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclohexanol (47 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (85 mg, yield 56%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.47-2.20 (m, 13H), 2.28 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.74 (brs, 1H), 6.43 (s, 1H), 6.57 (brs, 1H), 7.02 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 7.75 (brs, 1H), 8.14 (s, 1H), 8.49 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 451 (M⁺+1)

Example 223 2-Methylphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, o-cresol (55 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (116 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 432 (M⁺+1)

Example 224 Phenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, phenol (44 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (69 mg, yield 50%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.15 (s, 3H), 2.34 (s, 3H), 4.01 (s, 3H), 4.07 (s, 3H), 6.32 (d, J=5.4 Hz, 1H), 6.77 (brs, 1H), 6.97 (s, 1H), 7.22-7.28 (m, 3H), 7.40-7.47 (m, 3H), 7.60 (s, 1H), 7.85 (brs, 1H), 8.46 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 225 Benzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (134 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, phenylmethanol (49 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (100 mg, yield 72%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.00 (s, 6H), 5.17 (s, 2H), 7.12-7.37 (m, 9H), 7.44 (s, 1H), 8.24 (d, J=8.8 Hz, 1H), 8.56 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 226 3-Methoxybenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (3-methoxyphenyl)methanol (71 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (133 mg, yield 79%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.83 (s, 3H), 4.10 (s, 3H), 4.17 (s, 3H), 5.21 (s, 2H), 6.58 (brs, 1H), 6.88-7.01 (m, 4H), 7.18 (d, J=8.8 Hz, 1H), 7.29-7.33 (m, 1H), 7.61-7.63 (m, 3H), 8.14 (s, 1H), 8.50 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 462 (M⁺+1)

Example 227 2-Chlorobenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-chlorophenyl)methanol (73 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (153 mg, yield 90%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.03 (s, 3H), 4.04 (s, 3H), 5.27 (s, 2H), 6.83 (d, J=6.6 Hz, 1H), 7.35 (d, J=9.0 Hz, 2H), 7.41-7.43 (m, 2H), 7.52-7.54 (m, 1H), 7.58-7.61 (m, 2H), 7.69 (d, J=8.8 Hz, 2H), 7.74 (s, 1H), 8.77 (d, J=6.6 Hz, 1H), 10.12 (s, 1H)

Mass spectrometry value (ESI-MS, m/z) 466 (M⁺+1)

Example 228 3-Chlorobenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (3-chlorophenyl)methanol (73 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (158 mg, yield 93%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.03 (s, 3H), 4.04 (s, 3H), 5.20 (s, 2H), 6.82 (d, J=6.6 Hz, 1H), 7.35 (d, J=9.0 Hz, 2H), 7.42-7.47 (m, 3H), 7.52 (s, 1H), 7.63 (s, 1H), 7.69 (d, J=9.0 Hz, 2H), 7.74 (s, 1H), 8.78 (d, J=6.6 Hz, 1H), 10.09 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 466 (M⁺+1)

Example 229 4-Chlorobenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (4-chlorophenyl)methanol (73 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (147 mg, yield 86%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.03 (s, 3H), 4.04 (s, 3H), 5.18 (s, 2H), 6.82 (d, J=6.6 Hz, 1H), 7.35 (d, J=9.0 Hz, 2H), 7.48 (s, 4H), 7.64 (s, 1H), 7.68 (d, J=8.8 Hz, 2H), 7.74 (s, 1H), 8.78 (d, J=6.6 Hz, 1H), 10.07 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 466 (M⁺+1)

Example 230 Cyclohexyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclohexanol (51 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (120 mg, yield 77%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.24-1.58 (m, 6H), 1.73-1.76 (m, 2H), 1.90-1.94 (m, 2H), 4.02 (s, 3H), 4.04 (s, 3H), 4.54 (brs, 1H), 6.79 (d, J=6.3 Hz, 1H), 7.32 (d, J=9.0 Hz, 2H), 7.55 (s, 1H), 7.67 (d, J=9.0 Hz, 2H), 7.72 (s, 1H), 8.76 (d, J=6.6 Hz, 1H), 9.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 423 (M⁺+1)

Example 231 Benzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, phenylmethanol (55 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (130 mg, yield 82%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.03 (s, 3H), 4.04 (s, 3H), 5.19 (s, 2H), 6.82 (d, J=6.6 Hz, 1H), 7.30-7.46 (m, 7H), 7.62 (s, 1H), 7.69 (d, J=9.0. Hz, 2H), 7.74 (s, 1H), 8.78 (d, J=6.6 Hz, 1H), 10.04 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 431 (M⁺+1)

Example 232 2-Methylbenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methylphenyl)methanol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (140 mg, yield 89%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.07 (s, 3H), 2.20 (s, 3H), 2.36 (s, 3H), 4.05 (s, 6H), 5.17 (s, 2H), 6.67 (d, J=6.6 Hz, 1H), 7.13-7.27 (m, 4H), 7.39 (d, J=9.0 Hz, 2H), 7.62 (s, 1H), 7.79 (s, 1H), 8.76 (d, J=6.6 Hz, 1H), 9.22 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 473 (M⁺+1)

Example 233 3-Methylbenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (3-methylphenyl)methanol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (140 mg, yield 89%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.07 (s, 3H), 2.20 (s, 3H), 2.33 (s, 3H), 4.05 (s, 6H), 5.12 (s, 2H), 6.65 (d, J=6.8 Hz, 1H), 7.12-7.31 (m, 5H), 7.39 (d, J=8.8 Hz, 2H), 7.60 (s, 1H), 7.78 (s, 1H), 8.75 (d, J=6.8 Hz, 1H), 9.21 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 473 (M⁺+1)

Example 234 4-Methylbenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (4-methylphenyl)methanol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (40 mg, yield 25%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.07 (s, 3H), 2.19 (s, 3H), 2.32 (s, 3H), 4.04 (s, 6H), 5.11 (s, 2H), 6.65 (d, J=6.3 Hz, 1H), 7.14-7.22 (m, 3H), 7.32 (d, J=8.1 Hz, 2H), 7.38 (d, J=8.8 Hz, 1H), 7.56 (s, 1H), 7.78 (s, 1H), 8.75 (d, J=6.3 Hz, 1H), 9.19 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 473 (M⁺+1)

Example 235 2-Chlorobenzyl N-{4-[6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-chlorophenyl)methanol (67 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (127 mg, yield 77%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 2.27 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.36 (s, 2H), 6.55-6.56 (m, 2H), 7.03 (d, J=9.0 Hz, 1H), 7.25-7.33 (m, 1H), 7.43-7.50 (m, 2H), 7.67 (s, 1H), 8.15 (s, 1H), 8.48 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 236 3-Chlorobenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (3-chlorophenyl)methanol (67 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (147 mg, yield 90%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 2.27 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.21 (s, 2H), 6.56 (d, J=6.3 Hz, 2H), 7.03 (d, J=8.5 Hz, 1H), 7.25-7.35 (m, 3H), 7.43 (s, 1H), 7.67 (s, 1H), 7.75 (brs, 1H), 8.15 (s, 1H), 8.49 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 237 4-Chlorobenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (4-chlorophenyl)methanol (67 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (103 mg, yield 63%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 2.26 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.20 (s, 2H), 6.54 (brs, 2H), 7.03 (d, J=8.8 Hz, 1H), 7.38 (s, 4H), 7.66 (s, 1H), 7.71 (brs, 1H), 8.15 (s, 1H), 8.50 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 238 3-Methoxybenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (3-methoxyphenyl)methanol (65 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (136 mg, yield 84%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 2.26 (s, 3H), 3.84 (s, 3H), 4.11 (s, 3H), 4.18 (s, 3H), 5.21 (s, 2H), 6.55 (brs, 2H), 6.84-7.02 (m, 4H), 7.25-7.32 (m, 1H), 7.67 (s, 1H), 7.83 (brs, 1H), 8.16 (s, 1H), 8.44 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 489 (M⁺+1)

Example 239 2-Methoxybenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methoxyphenyl)methanol (65 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (130 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13 (s, 3H), 2.26 (s, 3H), 3.90 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.31 (s, 2H), 6.51 (s, 1H), 6.58 (d, J=6.6 Hz, 1H), 6.88-7.01 (m, 3H), 7.34-7.42 (m, 2H), 7.64 (s, 1H), 7.96 (s, 1H), 8.15 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 489 (M⁺+1)

Example 240 3-Methoxybenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (3-methoxyphenyl)methanol (65 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (120 mg, yield 74%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13 (s, 3H), 2.27 (s, 3H), 3.84 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.22 (s, 2H), 6.51 (s, 1H), 6.58 (d, J=6.3 Hz, 1H), 6.91-7.03 (m, 4H), 7.25-7.35 (m, 1H), 7.64 (s, 1H), 7.93 (s, 1H), 8.15 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 489 (M⁺+1)

Example 241 2-Chlorobenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-chlorophenyl)methanol (67 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (112 mg, yield 68%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13 (s, 3H), 2.28 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.36 (s, 2H), 6.54 (s, 1H), 6.58 (d, J=6.3 Hz, 1H), 6.96 (s, 1H), 7.26-7.33 (m, 2H), 7.43-7.49 (m, 2H), 7.64 (s, 1H), 7.93 (s, 1H), 8.15 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 242 3-Chlorobenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (3-chlorophenyl)methanol (67 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (117 mg, yield 71%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.14 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.21 (s, 2H), 6.53 (s, 1H), 6.56 (s, 1H), 6.96 (s, 1H), 7.26-7.38 (m, 3H), 7.44 (s, 1H), 7.64 (s, 1H), 7.91 (s, 1H), 8.15 (s, 1H), 8.43 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 243 4-Chlorobenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (4-chlorophenyl)methanol (67 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (154 mg, yield 94%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13 (s, 3H), 2.27 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.20 (s, 2H), 6.50 (s, 1H), 6.58 (s, 1H), 6.95 (s, 1H), 7.38 (s, 4H), 7.64 (s, 1H), 7.90 (s, 1H), 8.15 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 244 Propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-propanol (28 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (115 mg, yield 83%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.01 (t, J=7.3 Hz, 3H), 1.72-1.77 (m, 2H), 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.17 (t, J=7.8 Hz, 2H), 6.42 (s, 1H), 6.60 (brs, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.92 (s, 1H), 8.15 (s, 1H), 8.50 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 411 (M⁺+1)

Example 245 2-Methylbenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methylphenyl)methanol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (140 mg, yield 89%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13 (s, 3H), 2.26 (s, 3H), 2.43 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.27 (s, 2H), 6.50 (s, 1H), 6.58 (brs, 1H), 6.95 (s, 1H), 7.25-7.30 (m, 3H), 7.40 (d, J=7.1 Hz, 1H), 7.64 (s, 1H), 7.94 (s, 1H), 8.15 (s, 1H), 8.50 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 473 (M⁺+1)

Example 246 2-Naphthylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-naphthylmethanol (87 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (160 mg, yield 90%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.14 (s, 3H), 2.28 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.29 (s, 2H), 6.53 (s, 1H), 6.58 (s, 1H), 6.95 (s, 1H), 7.37-7.53 (m, 4H), 7.59-7.65 (m, 4H), 7.95 (s, 1H), 8.15 (s, 1H), 8.50 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 510 (M⁺+1)

Example 247 Propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-propanol (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (104 mg, yield 73%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.01 (t, J=7.6 Hz, 3H), 1.71-1.76 (m, 2H), 4.10 (s, 3H), 4.17 (s, 3H), 4.17 (t, J=8.1 Hz, 2H), 6.69 (brs, 1H), 6.81 (s, 1H), 7.18 (d, J=8.8 Hz, 2H), 7.61 (d, J=8.3 Hz, 2H), 7.64 (s, 1H), 8.14 (s, 1H), 8.50 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 383 (M⁺+1)

Example 248 2-Methoxybenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methoxyphenyl)methanol (71 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (123 mg, yield 73%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.89 (s, 3H), 4.10 (s, 3H), 4.17 (s, 3H), 5.30 (s, 2H), 6.69 (d, J=6.3 Hz, 1H), 6.83 (s, 1H), 6.93-7.00 (m, 2H), 7.18-7.52 (m, 4H), 7.59-7.63 (m, 3H), 8.15 (s, 1H), 8.49 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 462 (M⁺+1)

Example 249 4-Methoxybenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (4-methoxyphenyl)methanol (71 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (140 mg, yield 83%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.83 (s, 3H), 4.10 (s, 3H), 4.17 (s, 3H), 5.17 (s, 2H), 6.68 (d, J=6.3 Hz, 1H), 6.83 (s, 1H), 6.92 (d, J=8.5 Hz, 2H), 7.17 (d, J=9.0 Hz, 2H), 7.37 (d, J=8.5 Hz, 2H), 7.59 (d, J=9.0 Hz, 2H), 7.63 (s, 1H), 8.14 (s, 1H), 8.49 (t, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 462 (M⁺+1)

Example 250 2-Methylbenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methylphenyl)methanol (62 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (143 mg, yield 88%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.42 (s, 3H), 4.10 (s, 3H), 4.17 (s, 3H), 5.27 (s, 2H), 6.68 (d, J=6.3 Hz, 1H), 6.87 (s, 1H), 7.17-7.28 (m, 5H), 7.38 (d, J=7.1 Hz, 1H), 7.61 (d, J=9.0 Hz, 2H), 7.63 (s, 1H), 8.14 (s, 1H), 8.49 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 446 (M⁺+1)

Example 251 3-Methylbenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (3-methylphenyl)methanol (62 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (146 mg, yield 89%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.38 (s, 3H), 4.10 (s, 3H), 4.17 (s, 3H), 5.20 (s, 2H), 6.69 (brs, 1H), 6.92 (s, 1H), 7.17-7.31 (m, 6H), 7.61-7.63 (m, 3H), 8.14 (s, 1H), 8.51 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 446 (M⁺+1)

Example 252 4-Methylbenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (4-methylphenyl)methanol (62 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (133 mg, yield 81%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.37 (s, 3H), 4.10 (s, 3H), 4.17 (s, 3H), 5.20 (s, 2H), 6.69 (brs, 1H), 6.92 (s, 1H), 7.16-7.33 (m, 6H), 7.60 (d, J=7.3 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.49 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 446 (M⁺+1)

Example 253 2-Methylbenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methylphenyl)methanol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (122 mg, yield 77%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.26 (s, 3H), 2.43 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.27 (s, 2H), 6.52 (s, 1H), 6.58 (d, J=6.3 Hz, 1H), 6.95 (s, 1H), 7.24-7.30 (m, 3H), 7.40 (d, J=7.1 Hz, 1H), 7.65 (s, 1H), 7.93 (s, 1H), 8.15 (s, 1H), 8.49 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 254 3-Methylbenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (3-methylphenyl)methanol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (120 mg, yield 76%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13 (s, 3H), 2.27 (s, 3H), 2.39 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.21 (s, 2H), 6.53 (s, 1H), 6.58 (brs, 1H), 6.95 (s, 1H), 7.18-7.30 (m, 4H), 7.64 (s, 1H), 7.94 (s, 1H), 8.15 (s, 1H), 8.48 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 255 4-Methylbenzyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (4-methylphenyl)methanol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (139 mg, yield 88%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13 (s, 3H), 2.26 (s, 3H), 2.38 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.20 (s, 2H), 6.49 (s, 1H), 6.58 (brs, 1H), 6.94 (s, 1H), 7.22 (d, J=7.8 Hz, 2H), 7.34 (d, J=8.1 Hz, 2H), 7.64 (s, 1H), 7.94 (s, 1H), 8.15 (s, 1H), 8.50 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 256 Hexyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-hexanol (52 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (110 mg, yield 70%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.92 (t, J=6.8 Hz, 3H), 1.33-1.35 (m, 6H), 1.67-1.72 (m, 2H), 4.10 (s, 3H), 4.17 (s, 3H), 4.20 (t, J=6.8 Hz, 2H), 6.70 (d, J=6.3 Hz, 1H), 6.79 (s, 1H), 7.18 (d, J=9.0 Hz, 2H), 7.60 (d, J=8.8 Hz, 2H), 7.64 (s, 1H), 8.14 (s, 1H), 8.51 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 426 (M⁺+1)

Example 257 4-Butylphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-butylphenol (77 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (130 mg, yield 75%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.94 (t, J=7.3 Hz, 3H), 1.34-1.40 (m, 2H), 1.51-1.63 (m, 2H), 2.63 (t, J=7.8 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 6.71 (d, J=6.3 Hz, 1H), 7.09 (d, J=8.5 Hz, 2H), 7.20-7.23 (m, 4H), 7.64 (s, 1H), 7.69 (d, J=8.8 Hz, 2H), 8.15 (s, 1H), 8.52 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 258 1-Ethylbutyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-hexanol (52 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (130 mg, yield 83%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.95-0.98 (m, 6H), 1.39-1.67 (m, 6H), 4.11 (s, 3H), 4.17 (s, 3H), 4.84-4.86 (m, 1H), 6.70 (d, J=6.1 Hz, 1H), 6.77 (s, 1H), 7.18 (d, J=9.0 Hz, 2H), 7.61 (d, J=8.8 Hz, 2H), 7.64 (s, 1H), 8.13 (s, 1H), 8.53 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 426 (M⁺+1)

Example 259 4-(Tert-butyl)phenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-(tert-butyl)phenol (77 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (150 mg, yield 87%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.34 (s, 9H), 4.11 (s, 3H), 4.17 (s, 3H), 6.71 (d, J=6.1 Hz, 1H), 7.13 (d, J=8.8 Hz, 2H), 7.21-7.27 (m, 3H), 7.43 (d, J=8.8 Hz, 2H), 7.64 (s, 1H), 7.68 (d, J=8.8 Hz, 2H), 8.15 (s, 1H), 8.51 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 260 2-Methoxyphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (151 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-methoxyphenol (63 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (75 mg, yield 46%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.90 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 6.70 (brs, 1H), 6.85 (s, 1H), 6.92-7.02 (m, 4H), 7.15-7.25 (m, 3H), 7.64 (s, 1H), 7.70 (d, J=8.3 Hz, 1H), 8.14 (s, 1H), 8.52 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 448 (M⁺+1)

Example 261 Hexyl N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-hexanol (48 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (106 mg, yield 72%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.92 (t, J=7.1 Hz, 3H), 1.34-1.44 (m, 6H), 1.67-1.74 (m, 2H), 2.10 (s, 3H), 2.28 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.20 (t, J=6.8 Hz, 2H), 6.45 (s, 1H), 6.56 (d, J=6.6 Hz, 1H), 7.02 (d, J=9.0 Hz, 1H), 7.67 (s, 1H), 7.75 (d, J=9.3 Hz, 1H), 8.16 (s, 1H), 8.46 (t, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 454 (M⁺+1)

Example 262 Hexyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-hexanol (48 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (154 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.92 (t, J=7.1 Hz, 3H), 1.34-1.42 (m, 6H), 1.68-1.73 (m, 2H), 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.18 (S, 3H), 4.21 (t, J=6.8 Hz, 2H), 6.42 (s, 1H), 6.59 (brs, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.92 (s, 1H), 8.15 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 454 (M⁺+1)

Example 263 1-Phenylpropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-phenyl-1-propanol (35 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 92%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.6 Hz, 3H), 1.88-1.93 (m, 1H), 1.99-2.05 (m, 1H), 4.10 (s, 3H), 4.16 (s, 3H), 5.69 (t, J=7.3 Hz, 1H), 6.66 (d, J=5.6 Hz, 1H), 6.84 (s, 1H), 7.16 (d, J=8.8 Hz, 2H), 7.32-7.39 (m, 5H), 7.59 (d, J=8.8 Hz, 2H), 7.63 (s, 1H), 8.15 (d, J=4.1 Hz, 1H), 8.45-8.47 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 460 (M⁺+1)

Example 264 1-Phenylpropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-phenyl-1-propanol (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (76 mg, yield 97%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.97 (t, J=7.5 Hz, 3H), 1.89-1.94 (m, 1H), 2.01-2.17 (m, 1H), 2.10 (s, 3H), 2.28 (s, 3H), 4.10 (s, 3H), 4.17 (s, 3H), 5.68 (t, J=7.3 Hz, 1H), 6.50 (s, 1H), 6.55 (d, J=6.3 Hz, 1H), 6.93 (s, 1H), 7.33-7.39 (m, 5H), 7.64 (s, 1H), 7.91 (s, 1H), 8.14 (s, 1H), 8.45 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 265 1-Phenylpropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-phenyl-1-propanol (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (52 mg, yield 66%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.3 Hz, 3H), 1.89-1.92 (m, 1H), 1.94-2.05 (m, 1H), 2.09 (s, 3H), 2.25 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.69 (t, J=7.1 Hz, 1H), 6.52 (s, 1H), 6.54 (s, 1H), 6.99 (d, J=8.5 Hz, 1H), 7.32-7.39 (m, 5H), 7.66 (s, 1H), 7.73 (brs, 1H), 8.15 (s, 1H), 8.45 (t, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 266 4-Pentenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-penten-1-ol (22 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.80-1.83 (m, 2H), 2.16-2.20 (m, 2H), 4.10 (s, 3H), 4.17 (s, 3H), 4.23 (t, J=6.6 Hz, 2H), 5.02-5.10 (m, 2H), 5.83-5.85 (m, 1H), 6.69 (d, J=6.3 Hz, 1H), 6.76 (s, 1H), 7.18 (d, J=8.8 Hz, 2H), 7.60 (d, J=9.0 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.48 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 410 (M⁺+1)

Example 267 4-Pentenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-penten-1-ol (20 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (71 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.81-1.85 (m, 2H), 2.13 (s, 3H), 2.18-2.20 (m, 2H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.23 (t, J=6.6 Hz, 2H), 5.02-5.11 (m, 2H), 5.81-5.88 (m, 1H), 6.42 (s, 1H), 6.58 (d, J=6.3 Hz, 1H), 6.95 (s, 1H), 7.64 (s, 1H), 7.91 (s, 1H), 8.16 (s, 1H), 8.46 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 438 (M⁺+1)

Example 268 4-Pentenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-penten-1-ol (20 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (67 mg, yield 95%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.79-1.86 (m, 2H), 2.10 (s, 3H), 2.16-2.20 (m, 2H), 2.27 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 4.22 (t, J=6.6 Hz, 2H), 5.02-5.10 (m, 2H), 5.81-5.88 (m, 1H), 6.44 (s, 1H), 6.56 (d, J=6.6 Hz, 1H), 7.03 (d, J=8.5 Hz, 1H), 7.67 (s, 1H), 7.76 (brs, 1H), 8.16 (d, J=4.1 Hz, 1H), 8.45 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 438 (M⁺+1)

Example 269 2,6-Dimethylphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2,6-dimethylphenol (32 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (82 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.26 (s, 6H), 4.11 (s, 3H), 4.17 (s, 3H), 6.70 (d, J=7.6 Hz, 1H), 7.10 (s, 2H), 7.22-7.26 (m, 4H), 7.65 (s, 1H), 7.71 (d, J=8.5 Hz, 2H), 8.16 (d, J=4.1 Hz, 1H), 8.48 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 446 (M⁺+1)

Example 270 2,6-Dimethylphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2,6-dimethylphenol (28 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (76 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13 (s, 3H), 2.28 (s, 6H), 2.39 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 6.59 (d, J=5.9 Hz, 1H), 7.01 (s, 1H), 7.11 (s, 2H), 7.25-7.27 (m, 2H), 7.65 (s, 1H), 7.98 (brs, 1H), 8.16 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 271 2,6-Dimethylphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2,6-dimethylphenol (28 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 89%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.14 (s, 3H), 2.28 (s, 6H), 2.38 (s, 3H), 4.12 (s, 3H), 4.18 (s, 3H), 6.56 (d, J=6.8 Hz, 1H), 7.00-7.10 (m, 4H), 7.25-7.27 (m, 1H), 7.67 (s, 1H), 8.16 (s, 1H), 8.46 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 272 4-Butylphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-butylphenol (35 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (12 mg, yield 15%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.90-0.96 (m, 3H), 1.33-1.44 (m, 2H), 1.50-1.65 (m, 2H), 2.13 (s, 3H), 2.28 (s, 3H), 2.53 (t, J=7.8 Hz, 1H), 2.63 (t, J=8.1 Hz, 1H), 4.11 (s, 3H), 4.17 (s, 3H), 6.44 (s, 1H), 6.58 (d, J=6.3 Hz, 1H), 6.75 (d, J=8.5 Hz, 1H), 6.95 (s, 1H), 7.02 (t, J=8.5 Hz, 1H), 7.11 (d, J=8.5 Hz, 1H), 7.22 (d, J=8.8 Hz, 1H), 7.64 (s, 1H), 7.89 (brs, 1H), 8.16 (s, 1H), 8.45 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 273 4-Butylphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-butylphenol (35 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (44 mg, yield 55%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.94 (t, J=7.3 Hz, 3H), 1.34-1.44 (m, 2H), 1.56-1.63 (m, 2H), 2.13 (s, 3H), 2.36 (s, 3H), 2.63 (t, J=7.8 Hz, 2H), 4.12 (s, 3H), 4.17 (s, 3H), 6.57 (d, J=10.7 Hz, 1H), 7.04-7.26 (m, 6H), 7.67 (s, 1H), 7.84 (brs, 1H), 8.17 (d, J=4.4 Hz, 1H), 8.46 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 274 4-(Tert-butyl)phenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-(tert-butyl)phenol (35 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (35 mg, yield 44%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.54 (s, 9H), 2.13 (s, 3H), 2.37 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 6.59 (s, 1H), 6.77 (d, J=8.8 Hz, 1H), 6.95 (s, 1H), 7.00 (s, 1H), 7.14 (d, J=8.8 Hz, 2H), 7.43 (d, J=8.8 Hz, 2H), 7.65 (s, 1H), 7.99 (brs, 1H), 8.16 (s, 1H), 8.46 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 275 4-(Tert-butyl)phenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-(tert-butyl)phenol (35 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (34 mg, yield 42%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.54 (s, 9H), 2.13 (s, 3H), 2.36 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 6.57 (d, J=5.6 Hz, 1H), 6.77 (d, J=8.8 Hz, 1H), 7.05 (d, J=9.3 Hz, 1H), 7.14 (d, J=8.8 Hz, 2H), 7.42 (d, J=8.8 Hz, 2H), 7.67 (s, 1H), 7.84 (brs, 1H), 8.17 (d, J=3.9 Hz, 1H), 8.45 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 276 1-Ethylbutyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-hexanol (24 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (20 mg, yield 27%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.95-0.99 (m, 6H), 1.40-1.65 (m, 6H), 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.85 (brs, 1H), 6.41 (s, 1H), 6.57 (d, J=4.6 Hz, 1H), 6.94 (s, 1H), 7.65 (s, 1H), 7.96 (s, 1H), 8.15 (s, 1H), 8.45 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 454 (M⁺+1)

Example 277 1-Ethylbutyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-hexanol (24 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (39 mg, yield 53%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.94-0.99 (m, 6H), 1.40-1.68 (m, 6H), 2.10 (s, 3H), 2.28 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 4.85 (brs, 1H), 6.55 (d, J=5.9 Hz, 1H), 7.00-7.03 (m, 1H), 7.79 (s, 1H), 8.16-8.17 (m, 1H), 8.44 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 454 (M⁺+1)

Example 278 2-Methoxyphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-methoxyphenol (29 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (39 mg, yield 51%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.12 (s, 3H), 2.38 (s, 3H), 3.90 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 6.60 (d, J=5.9 Hz, 1H), 6.86-7.04 (m, 4H), 7.17-7.19 (m, 1H), 7.65 (s, 1H), 7.99 (s, 1H), 8.16 (d, J=4.1 Hz, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 476 (M⁺+1)

Example 279 2-Methoxyphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-methoxyphenol (29 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (31 mg, yield 41%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13 (s, 3H), 2.37 (s, 3H), 3.89 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 6.57 (brs, 1H), 6.86-7.06 (m, 5H), 7.18 (d, J=6.3 Hz, 1H), 7.67 (d, J=2.0 Hz, 1H), 8.17 (d, J=3.9 Hz, 1H), 8.46 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 476 (M⁺+1)

Example 280 2,6-Dimethoxyphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2,6-dimethoxyphenol (40 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 92%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.87 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 6.60-6.67 (m, 4H), 7.17-7.21 (m, 2H), 7.64 (s, 1H), 7.70 (d, J=8.8 Hz, 2H), 8.15 (s, 1H), 8.49 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 478 (M⁺+1)

Example 281 2,6-Dimethoxyphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2,6-dimethoxyphenol (35 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (75 mg, yield 93%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.33 (s, 3H), 2.38 (s, 3H), 3.89 (s, 6H), 4.11 (s, 3H), 4.17 (s, 3H), 6.60 (brs, 1H), 6.67 (d, J=8.5 Hz, 1H), 6.98-7.19 (m, 2H), 7.65 (s, 1H), 8.04 (s, 1H), 8.15 (s, 1H), 8.48 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 282 2,6-Dimethoxyphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2,6-dimethoxyphenol (35 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (74 mg, yield 91%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.21 (s, 3H), 2.37 (s, 3H), 3.88 (s, 3H), 3.89 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 6.58-6.60 (m, 2H), 6.66 (d, J=8.5 Hz, 1H), 6.78-6.82 (m, 1H), 7.02-7.05 (m, 1H), 7.16-7.20 (m, 1H), 7.67 (s, 1H), 7.87 (s, 1H), 8.16 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 283 Cyclohexylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclohexylmethanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (49 mg, yield 61%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.03-1.04 (m, 2H), 1.21-1.27 (m, 4H), 1.78-1.80 (m, 5H), 4.02 (d, J=6.3 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 6.70 (d, J=5.9 Hz, 1H), 6.88 (s, 1H), 7.18 (d, J=8.8 Hz, 2H), 7.61 (d, J=8.5 Hz, 2H), 7.64 (s, 1H), 8.15 (d, J=4.1 Hz, 1H), 8.47 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 438 (M⁺+1)

Example 284 Cyclohexylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclohexylmethanol (26 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 83%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.02-1.04 (m, 2H), 1.21-1.31 (m, 4H), 1.72-1.79 (m, 5H), 2.13 (s, 3H), 2.29 (s, 3H), 4.03 (d, J=6.3 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 6.42 (s, 1H), 6.58 (d, J=4.9 Hz, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.93 (s, 1H), 8.16 (d, J=4.1 Hz, 1H), 8.46 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 466 (M⁺+1)

Example 285 Cyclohexylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclohexylmethanol (26 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 64%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.97-1.07 (m, 2H), 1.17-1.32 (m, 4H), 1.69-1.82 (m, 5H), 2.10 (s, 3H), 2.28 (s, 3H), 4.02 (d, J=6.6 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 6.44 (s, 1H), 6.55 (d, J=5.4 Hz, 1H), 7.00-7.04 (m, 2H), 7.67 (s, 1H), 7.77 (brs, 1H), 8.16 (d, J=4.1 Hz, 1H), 8.44 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 466 (M⁺+1)

Example 286 Cycloheptyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cycloheptanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 85%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.47-1.79 (m, 12H), 4.10 (s, 3H), 4.17 (s, 3H), 4.90-4.96 (m, 1H), 6.70 (d, J=5.9 Hz, 1H), 6.83 (s, 1H), 7.17 (d, J=9.0 Hz, 2H), 7.60 (d, J=8.5 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 438 (M⁺+1)

Example 287 Cycloheptyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cycloheptanol (26 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 91%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.51-1.74 (m, 12H), 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.96 (brs, 1H), 6.40 (s, 1H), 6.58 (d, J=6.3 Hz, 1H), 6.94 (s, 1H), 7.65 (s, 1H), 7.95 (s, 1H), 8.16 (d, J=4.1 Hz, 1H), 8.46 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 466 (M⁺+1)

Example 288 Cycloheptyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cycloheptanol (26 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (66 mg, yield 88%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.51-1.74 (m, 12H), 2.10 (s, 3H), 2.27 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 4.96 (brs, 1H), 6.43 (s, 1H), 6.56 (d, J=6.6 Hz, 1H), 7.02 (d, J=9.3 Hz, 1H), 7.67 (s, 1H), 7.78 (s, 1H), 8.16 (d, J=3.9 Hz, 1H), 8.45 (brs, 1H).

Mass spectrometry value (ESI-MS, m/z): 466 (M⁺+1)

Example 289 2-Methylphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, o-cresol (25 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 84%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13 (s, 3H), 2.31 (s, 3H), 2.39 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 6.60 (d, J=6.3 Hz, 1H), 6.85 (s, 1H), 7.00 (s, 1H), 7.14-7.27 (m, 4H), 7.65 (s, 1H), 7.98 (brs, 1H), 8.15 (d, J=3.7 Hz, 1H), 8.52 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 460 (M⁺+1)

Example 290 3-Methoxyphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-methoxyphenol (29 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (30 mg, yield 39%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.14 (s, 3H), 2.37 (s, 3H), 3.83 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 6.42 (s, 1H), 6.59 (brs, 1H), 6.79-6.84 (m, 3H), 7.00 (s, 1H), 7.30-7.34 (m, 1H), 7.65 (s, 1H), 7.98 (brs, 1H), 8.16 (s, 1H), 8.49 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 476 (M⁺+1)

Example 291 3-Methoxyphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-methoxyphenol (29 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (23 mg, yield 30%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13 (s, 3H), 2.36 (s, 3H), 3.83 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 6.44-6.48 (m, 1H), 6.56-6.58 (m, 1H), 6.78-6.83 (m, 3H), 7.06 (d, J=8.8 Hz, 1H), 7.29-7.33 (m, 1H), 7.67 (s, 1H), 7.81 (brs, 1H), 8.16 (d, J=3.4 Hz, 1H), 8.50 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 476 (M⁺+1)

Example 292 1,2,3,4-Tetrahydro-2-naphthalenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1,2,3,4-tetrahydro-2-naphthalenol (34 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.08-2.13 (m, 2H), 2.12 (s, 3H), 2.27 (s, 3H), 2.80-3.24 (m, 4H), 4.11 (s, 3H), 4.17 (s, 3H), 5.30 (brs, 1H), 6.43 (s, 1H), 6.57 (d, J=6.6 Hz, 1H), 6.94 (s, 1H), 7.11-7.18 (m, 4H), 7.64 (s, 1H), 7.94 (brs, 1H), 8.15 (d, J=3.9 Hz, 1H), 8.48 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 500 (M⁺+1)

Example 293 1,2,3,4-Tetrahydro-2-naphthalenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1,2,3,4-tetrahydro-2-naphthalenol (34 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (55 mg, yield 69%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.08-2.13 (m, 2H), 2.09 (s, 3H), 2.25 (s, 3H), 2.92-3.23 (m, 4H), 4.11 (s, 3H), 4.17 (s, 3H), 5.29 (brs, 1H), 6.46 (s, 1H), 6.55 (d, J=6.1 Hz, 1H), 7.01 (d, J=8.8 Hz, 1H), 7.12-7.18 (m, 4H), 7.67 (s, 1H), 7.77 (brs, 1H), 8.16 (d, J=3.7 Hz, 1H), 8.48 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 500 (M⁺+1)

Example 294 4-Phenylphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-phenylphenol (44 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (29 mg, yield 32%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.11 (s, 3H), 4.17 (s, 3H), 6.71 (s, 1H), 6.93 (d, J=8.5 Hz, 1H), 7.26-7.78 (m, 13H), 8.14 (brs, 1H), 8.53 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 295 4-Phenylphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-phenylphenol (39 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (55 mg, yield 66%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.14 (s, 3H), 2.28 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 6.44 (s, 1H), 6.60 (brs, 1H), 6.95 (s, 1H), 7.01 (brs, 1H), 7.26-7.52 (m, 4H), 7.57-7.65 (m, 5H), 7.89 (s, 1H), 8.15 (brs, 1H), 8.48 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 522 (M⁺+1)

Example 296 4-Phenylphenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-phenylphenol (39 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (36 mg, yield 43%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.14 (s, 3H), 2.38 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 6.57-6.59 (m, 1H), 6.92-7.08 (m, 2H), 7.25-7.79 (m, 10H), 8.16-8.17 (m, 1H), 8.47-8.52 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 522 (M⁺+1)

Example 297 Phenethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-phenyl-1-ethanol (32 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (42 mg, yield 51%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.03 (t, J=6.8 Hz, 2H), 4.10 (s, 3H), 4.17 (s, 3H), 4.45 (t, J=7.1 Hz, 2H), 6.69 (s, 1H), 6.78 (s, 1H), 7.16-7.36 (m, 7H), 7.52-7.64 (m, 3H), 8.15 (s, 1H), 8.49 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 446 (M⁺+1)

Example 298 Phenethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-phenyl-1-ethanol (28 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (76 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.12 (s, 3H), 2.26 (s, 3H), 3.04 (t, J=6.8 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 4.44 (t, J=7.1 Hz, 2H), 6.40 (s, 1H), 6.59 (s, 1H), 6.95 (s, 1H), 7.26-7.36 (m, 5H), 7.64 (s, 1H), 7.86 (brs, 1H), 8.16 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 299 Phenethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-phenyl-1-ethanol (28 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 79%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ2.09 (s, 3H), 2.24 (s, 3H), 3.03 (t, J=6.8 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 4.44 (t, J=7.1 Hz, 2H), 6.42 (s, 1H), 6.55 (d, J=5.9 Hz, 1H), 7.01 (d, J=8.5 Hz, 1H), 7.26-7.36 (m, 5H), 7.66 (s, 1H), 8.16 (d, J=4.1 Hz, 1H), 8.46 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 300 2-(Tert-butyl)phenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-(tert-butyl)phenol (39 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (64 mg, yield 74%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.42 (s, 9H), 4.11 (s, 3H), 4.17 (s, 3H), 6.72 (brs, 1H), 7.11 (d, J=6.3 Hz, 1H), 7.22-7.26 (m, 6H), 7.43-7.45 (m, 1H), 7.65 (s, 1H), 7.71 (brs, 1H), 8.15 (brs, 1H), 8.51 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 301 2-(Tert-butyl)phenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-(tert-butyl)phenol (35 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 96%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.56 (s, 9H), 2.13 (s, 3H), 2.39 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 6.59 (brs, 1H), 7.01 (s, 1H), 7.13 (d, J=7.8 Hz, 1H), 7.21-7.26 (m, 3H), 7.43-7.45 (m, 1H), 7.65 (s, 1H), 8.15 (s, 1H), 8.49 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 302 2-(Tert-butyl)phenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-(tert-butyl)phenol (35 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 60%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.56 (s, 9H), 2.14 (s, 3H), 2.38 (s, 3H), 4.12 (s, 3H), 4.18 (s, 3H), 6.55 (brs, 1H), 7.06 (d, J=9.0 Hz, 1H), 7.14 (d, J=7.8 Hz, 1H), 7.21-7.26 (m, 4H), 7.42 (brs, 1H), 7.67 (s, 1H), 8.16 (s, 1H), 8.48 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 303 2-Piperidinoethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-piperidino-1-ethanol (34 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (66 mg, yield 74%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.89-1.93 (m, 4H), 2.29-2.45 (m, 2H), 2.74-2.86 (m, 2H), 3.36 (brs, 1H), 3.70-3.73 (m, 2H), 4.10 (s, 3H), 4.16 (s, 3H), 4.56-4.58 (m, 2H), 6.72 (d, J=6.3 Hz, 1H), 7.15 (d, J=8.8 Hz, 2H), 7.65 (s, 1H), 7.74 (d, J=8.8 Hz, 2H), 8.10 (s, 1H), 8.52 (t, J=6.3 Hz, 1H), 9.60 (brs, 1H), 11.42 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 453 (M⁺+1)

Example 304 2-Piperidinoethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-piperidino-1-ethanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (42 mg, yield 51%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.50 (brs, 2H), 1.85 (brs, 2H), 2.11 (s, 3H), 2.43 (brs, 5H), 2.78 (brs, 2H), 3.34 (brs, 2H), 3.70 (brs, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 4.56 (brs, 2H), 6.61 (brs, 1H), 6.95 (s, 1H), 7.66 (s, 1H), 7.86 (s, 1H), 8.13 (s, 1H), 8.48 (brs, 1H), 11.85 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 305 2-Piperidinoethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-piperidino-1-ethanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (83 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.88 (brs, 2H), 2.09 (s, 3H), 2.31-2.39 (m, 1H), 2.39 (s, 3H), 2.47-2.51 (m, 1H), 2.71-2.80 (m, 2H), 3.12-3.14 (m, 1H), 3.33 (brs, 2H), 3.69 (brs, 2H), 4.01-4.03 (m, 1H), 4.12 (s, 3H), 4.17 (s, 3H), 4.54-4.55 (m, 2H), 6.58 (d, J=6.3 Hz, 1H), 6.98 (d, J=8.8 Hz, 1H), 7.68 (s, 1H), 7.76 (d, J=9.0 Hz, 1H), 8.14 (s, 1H), 8.48-8.49 (m, 1H), 11.83 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 306 2-Morpholinoethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-morpholino-1-ethanol (34 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (43 mg, yield 48%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.11 (brs, 2H)—, 3.42 (brs, 2H), 3.66 (brs, 2H), 4.01-4.19 (m, 2H), 4.10 (s, 3H), 4.16 (s, 3H), 4.46 (brs, 2H), 4.62 (brs, 2H), 6.73 (s, 1H), 7.14 (s, 1H), 7.65 (s, 1H), 7.73 (s, 2H), 8.09 (s, 1H), 8.54 (brs, 1H), 9.45 (s, 1H), 12.38 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 455 (M⁺+1)

Example 307 2-Morpholinoethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-morpholino-1-ethanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (63 mg, yield 76%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.11 (s, 3H), 2.42 (s, 3H), 3.06 (brs, 2H), 3.41 (brs, 2H), 3.62 (brs, 2H), 4.02-4.17 (m, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 4.52-4.59 (m, 4H), 6.60 (brs, 1H), 6.95 (s, 1H), 7.66 (s, 1H), 7.85 (s, 1H), 8.13 (s, 2H), 8.30 (brs, 1H), 8.50 (brs, 1H), 12.79 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 483 (M⁺+1)

Example 308 2-Morpholinoethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-morpholino-1-ethanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (74 mg, yield 89%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.09 (s, 3H), 2.39 (s, 3H), 3.03 (brs, 2H), 3.38 (brs, 2H), 3.62 (d, J=11.7 Hz, 2H), 4.02-4.04 (m, 2H), 4.12 (s, 3H), 4.17 (s, 3H), 4.50-4.59 (m, 4H), 6.57 (d, J=6.3 Hz, 1H), 6.99 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 7.77 (d, J=9.3 Hz, 1H), 8.14 (s, 1H), 8.32 (brs, 1H), 8.48 (s, 1H), 12.87 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 483 (M⁺+1)

Example 309 6-(Dimethylamino)hexyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 6-(dimethylamino)-1-hexanol (38 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (31 mg, yield 34%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.43-1.87 (m, 8H), 2.82-3.08 (m, 8H), 4.11 (s, 3H), 4.16 (s, 3H), 4.11-4.22 (m, 2H), 6.72 (s, 1H), 7.14 (s, 2H), 7.65 (s, 1H), 7.87 (s, 2H), 8.11 (s, 1H), 8.50 (brs, 1H), 8.80 (brs, 1H), 12.00 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 469 (M⁺+1)

Example 310 6-(Dimethylamino)hexyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 6-(dimethylamino)-1-hexanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 56%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.53-1.93 (m, 8H), 2.13 (s, 3H), 2.33 (s, 3H), 2.83 (s, 6H), 3.02 (brs, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 4.11-4.21 (m, 2H), 6.61 (brs, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.85 (s, 1H), 8.14 (s, 1H), 8.49 (brs, 1H), 12.39 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 311 6-(Dimethylamino)hexyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 6-(dimethylamino)-1-hexanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (66 mg, yield 77%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.75-2.01 (m, 8H), 2.10 (s, 3H), 2.31 (s, 3H), 2.83 (s, 6H), 3.03 (s, 2H), 4.12 (s, 3H), 4.17 (s, 3H), 4.12-4.21 (m, 2H), 6.59 (s, 1H), 7.01 (d, J=8.1 Hz, 1H), 7.68 (s, 1H), 8.13 (s, 1H), 8.50 (brs, 1H), 12.02 (brs, 1H), 12.30 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 312 Cyclohexyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclohexanol (26 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 71%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.21-1.57 (m, 6H), 1.76 (brs, 2H), 1.94 (brs, 2H), 4.12 (s, 3H), 4.19 (s, 3H), 4.78 (brs, 1H), 6.72 (s, 1H), 7.19 (d, J=9.0 Hz, 2H), 7.57 (d, J=8.8. Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 425 (M⁺+1)

Example 313 Cyclohexyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclohexanol (23 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 77%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.30-1.58 (m, 6H), 1.78 (brs, 2H), 1.95 (brs, 2H), 4.12 (s, 3H), 4.20 (s, 3H), 4.79 (brs, 1H), 7.16-7.20 (m, 2H), 7.32 (s, 1H), 7.59 (s, 1H), 8.17 (s, 1H), 8.40 (d, J=9.3 Hz, 1H), 8.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 459 (M⁺+1)

Example 314 Propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-propanol (16 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.00 (t, J=7.3 Hz, 3H), 1.68-1.75 (m, 2H), 4.12 (s, 3H), 4.16 (t, J=6.8 Hz, 2H), 4.19 (s, 3H), 6.77 (s, 1H), 7.20 (d, J=9.0 Hz, 2H), 7.58 (d, J=8.8 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.81 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 384 (M⁺+1)

Example 315 2-Methoxybenzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methoxyphenyl)methanol (36 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (91 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.88 (s, 3H), 4.12 (s, 3H), 4.19 (s, 3H), 5.29 (s, 2H), 6.84 (s, 1H), 6.92-7.00 (m, 2H), 7.19 (d, J=9.0 Hz, 2H), 7.33-7.40 (m, 2H), 7.57 (d, J=9.0 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 463 (M⁺+1)

Example 316 2-Methoxybenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methoxyphenyl)methanol (32 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (79 mg, yield 93%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.89 (s, 3H), 4.12 (s, 3H), 4.20 (s, 3H), 5.32 (s, 2H), 6.89 (s, 2H), 6.89-7.01 (m, 3H), 7.18-7.21 (m, 1H), 7.29-7.43 (m, 3H), 7.59 (s, 1H), 8.16 (s, 1H), 8.43 (d, J=9.0 Hz, 1H), 8.83 (s, 1H), 9.57 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 317 2-Chlorobenzyl N-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-chlorophenyl)methanol (37 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (92 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.12 (s, 3H), 4.19 (s, 3H), 5.35 (s, 2H), 7.20 (d, J=9.0 Hz, 2H), 7.29-7.32 (m, 2H), 7.42-7.44 (m, 1H), 7.48-7.52 (m, 1H), 7.59 (d, J=8.8 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.79 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 318 2-Chlorobenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-chlorophenyl)methanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 93%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.12 (s, 3H), 4.20 (s, 3H), 5.38 (s, 2H), 7.19-7.22 (m, 1H), 7.30-7.35 (m, 3H), 7.43-7.45 (m, 1H), 7.49-7.51 (m, 1H), 7.59 (s, 1H), 8.16 (s, 1H), 8.41 (d, J=9.0 Hz, 1H), 8.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 501 (M⁺+1)

Example 319 2-Methylbenzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methylphenyl)methanol (32 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (79 mg, yield 90%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.41 (s, 3H), 4.12 (s, 3H), 4.19 (s, 3H), 5.26 (s, 2H), 6.87 (s, 1H), 7.20 (d, J=9.0 Hz, 2H), 7.22-7.30 (m, 3H), 7.37-7.39 (m, 1H), 7.58 (d, J=8.8 Hz, 2H), 7.61 (s, 1H), 8.15 (s, 1H), 8.79 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 447 (M⁺+1)

Example 320 2-Methylbenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methylphenyl)methanol (28 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 75%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.43 (s, 3H), 4.12 (s, 3H), 4.20 (s, 3H), 5.28 (s, 2H), 7.18-7.33 (m, 5H), 7.40 (d, J=6.8 Hz, 1H), 7.59 (s, 1H), 8.16 (s, 1H), 8.41 (d, J=9.0 Hz, 1H), 8.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 321 Butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-butanol (19 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (34 mg, yield 46%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.97 (t, J=7.3 Hz, 3H), 1.41-1.49 (m, 2H), 1.62-1.72 (m, 2H), 4.10 (s, 3H), 4.17 (s, 3H), 4.21 (t, J=6.8 Hz, 2H), 6.70 (d, J=6.3 Hz, 1H), 6.85 (s, 1H), 7.18 (d, J=8.8 Hz, 2H), 7.61 (d, J=8.8 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 397 (M⁺+1)

Example 322 Butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy)-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-butanol (17 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (65 mg, yield 94%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.99 (t, J=7.3 Hz, 3H), 1.41-1.50 (m, 2H), 1.67-1.74 (m, 2H), 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.22 (t, J=6.8 Hz, 2H), 6.42 (s, 1H), 6.59 (brs, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.92 (s, 1H), 8.16 (s, 1H), 8.46 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 426 (M⁺+1)

Example 323 Butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-butanol (17 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 87%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.98 (t, J=7.3 Hz, 3H), 1.40-1.49 (m, 2H), 1.67-1.73 (m, 2H), 2.10 (s, 3H), 2.28 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 4.21 (t, J=6.8. Hz, 2H), 6.46 (s, 1H), 6.56 (d, J=6.3 Hz, 1H), 7.02 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 7.76 (d, J=8.5 Hz, 1H), 8.15 (s, 1H), 8.47 (t, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 426 (M⁺+1)

Example 324 Isopropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-propanol (16 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (42 mg, yield 59%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.33 (d, J=6.3 Hz, 6H), 4.11 (s, 3H), 4.17 (s, 3H), 5.02-5.09 (m, 1H), 6.70 (d, J=6.1 Hz, 1H), 6.74 (s, 1H), 7.18 (d, J=9.0 Hz, 1H), 7.60 (d, J=8.8 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 383 (M⁺+1)

Example 325 Isopropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-propanol (14 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (50 mg, yield 75%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.34 (d, J=6.3 Hz, 6H), 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.04-5.07 (m, 1H), 6.38 (s, 1H), 6.58 (brs, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.95 (s, 1H), 8.15 (s, 1H), 8.46 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 412 (M⁺+1)

Example 326 Octadecyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-octadecanol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (54 mg, yield 51%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.88 (t, J=7.1 Hz, 3H), 1.20-1.45 (m, 30H), 1.68-1.72 (m, 2H), 4.10 (s, 3H), 4.17 (s, 3H), 4.20 (t, J=6.6 Hz, 2H), 6.69 (d, J=6.3 Hz, 1H), 6.77 (s, 1H), 7.18 (d, J=8.8 Hz, 2H), 7.60 (d, J=8.8 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 594 (M⁺+1)

Example 327 Octadecyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-octadecanol (62 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (83 mg, yield 84%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.88 (t, J=7.1 Hz, 3H), 1.26-1.42 (m, 30H), 1.67-1.73 (m, 2H), 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.20 (t, J=6.6 Hz, 2H), 6.42 (s, 1H), 6.59 (brs, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.92 (s, 1H), 8.15 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 622 (M⁺+1)

Example 328 Octadecyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-octadecanol (62 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (96 mg, yield 97%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.88 (t, J=6.8 Hz, 3H), 1.21-1.42 (m, 30H), 1.67-1.72 (m, 2H), 2.10 (s, 3H), 2.27 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.20 (t, J=6.8 Hz, 2H), 6.44 (s, 1H), 6.56 (d, J=6.6 Hz, 1H), 7.02 (d, J=8.5 Hz, 1H), 7.67 (s, 1H), 7.75 (brs, 1H), 8.15 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 622 (M⁺+1)

Example 329 1-Ethylpentyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-heptanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (46 mg, yield 57%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.90-0.98 (m, 6H), 1.35-1.36 (m, 4H), 1.62-1.69 (m, 4H), 4.11 (s, 3H), 4.17 (s, 3H), 4.80-4.86 (m, 1H), 6.69 (d, J=6.3 Hz, 1H), 6.79 (s, 1H), 7.18 (d, J=8.8 Hz, 2H), 7.62 (d, J=9.0 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.47 (t, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 440 (M⁺+1)

Example 330 1-Ethylpentyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-heptanol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (59 mg, yield 78%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.93-0.99 (m, 6H), 1.30-1.45 (m, 4H), 1.57-1.68 (m, 4H), 2.13 (s, 3H), 2.30 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.82-4.85 (m, 1H), 6.42 (s, 1H), 6.58 (d, J=6.3 Hz, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.96 (s, 1H), 8.15 (s, 1H), 8.46 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 331 1-Ethylpentyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-heptanol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (46 mg, yield 61%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.91-0.99 (m, 6H), 1.30-1.45 (m, 4H), 1.59-1.68 (m, 4H), 2.10 (s, 3H), 2.28 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 4.82-4.84 (m, 1H), 6.43 (s, 1H), 6.55 (d, J=6.6 Hz, 1H), 7.02 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 7.78 (brs, 1H), 8.15 (s, 1H), 8.47 (t, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 332 1-Propylbutyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-heptanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 60%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.95 (t, J=7.3 Hz, 6H), 1.37-1.45 (m, 4H), 1.53-1.63 (m, 4H), 4.11 (s, 3H), 4.17 (s, 3H), 4.89-4.94 (m, 1H), 6.69 (d, J=6.6 Hz, 1H), 6.76 (s, 1H), 7.18 (d, J=8.8 Hz, 2H), 7.61 (d, J=8.8 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.47 (t, J=6.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 440 (M⁺+1)

Example 333 1-Propylbutyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-heptanol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (57 mg, yield 76%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.3 Hz, 6H), 1.38-1.46 (m, 4H), 1.54-1.64 (m, 4H), 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.91-4.94 (m, 1H), 6.41 (s, 1H), 6.57 (d, J=6.3 Hz, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.96 (s, 1H), 8.15 (s, 1H), 8.46 (t, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 334 1-Propylbutyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-heptanol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (44 mg, yield 58%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.1 Hz, 6H), 1.37-1.45 (m, 4H), 1.57-1.64 (m, 4H), 2.10 (s, 3H), 2.27 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 4.90-4.93 (m, 1H), 6.42 (s, 1H), 6.55 (d, J=6.3 Hz, 1H), 7.02 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 7.78 (brs, 1H), 8.15 (s, 1H), 8.45 (t, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 335 Hexyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-hexanol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (69 mg, yield 82%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.91 (t, J=7.1 Hz, 3H), 1.31-1.49 (m, 6H), 1.66-1.73 (m, 2H), 4.12 (s, 3H), 4.19 (s, 3H), 4.19 (t, J=7.1 Hz, 2H), 6.79 (s, 1H), 7.20 (d, J=8.8 Hz, 2H), 7.58 (d, J=8.8 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.79 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 427 (M⁺+1)

Example 336 Hexyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-hexanol (24 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (54 mg, yield 68%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.92 (t, J=7.1 Hz, 3H), 1.32-1.49 (m, 6H), 1.68-1.75 (m, 2H), 4.12 (s, 3H), 4.20 (s, 3H), 4.22 (t, J=6.8 Hz, 2H), 7.18 (d, J=2.4 Hz, 1H), 7.21 (d, J=2.7 Hz, 1H), 7.33 (d, J=2.7 Hz, 1H), 7.59 (s, 1H), 8.16 (s, 1H), 8.39 (d, J=9.0 Hz, 1H), 8.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 461 (M⁺+1)

Example 337 1-Ethylbutyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-hexanol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 73%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.93-0.97 (m, 6H), 1.36-1.68 (m, 6H), 4.13 (s, 3H), 4.19 (s, 3H), 4.82-4.87 (m, 1H), 6.75 (s, 1H), 7.20 (d, J=9.0 Hz, 2H), 7.59 (d, J=8.8 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 427 (M⁺+1)

Example 338 1-Ethylbutyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-hexanol (24 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (55 mg, yield 69%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.94-0.99 (m, 6H), 1.37-1.70 (m, 6H), 4.12 (s, 3H), 4.20 (s, 3H), 4.83-4.87 (m, 1H), 7.18 (d, J=2.7 Hz, 1H), 7.20 (d, J=2.7 Hz, 1H), 7.33 (d, J=2.7 Hz, 1H), 7.59 (s, 1H), 8.16 (s, 1H), 8.42 (d, J=9.3 Hz, 1H), 8.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 461 (M⁺+1)

Example 339 Phenethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-phenyl-1-ethanol (28 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (18 mg, yield 22%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.03 (t, J=7.1 Hz, 2H), 4.12 (s, 3H), 4.20 (s, 3H), 4.45 (t, J=7.1 Hz, 2H), 7.17 (d, J=2.4 Hz, 1H), 7.20 (d, J=2.7 Hz, 1H), 7.29-7.34 (m, 6H), 7.58 (s, 1H), 8.16 (s, 1H), 8.33 (brs, 1H), 8.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 340 Cyclohexylmethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclohexylmethanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 70%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.00-1.06 (m, 2H), 1.17-1.29 (m, 3H), 1.69-1.79 (m, 6H), 4.01 (d, J=6.3 Hz, 2H), 4.12 (s, 3H), 4.19 (s, 3H), 6.80 (s, 1H), 7.19 (d, J=9.0 Hz, 2H), 7.58 (d, J=8.8 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.79 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 439 (M⁺+1)

Example 341 Cyclohexylmethyl N-[2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclohexylmethanol (26 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (54 mg, yield 66%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.01-1.07 (m, 2H), 1.18-1.31 (m, 3H), 1.70-1.82 (m, 6H), 4.04 (d, J=6.3 Hz, 2H), 4.12 (s, 3H), 4.20 (s, 3H), 7.18 (d, J=2.7 Hz, 1H), 7.21 (d, J=2.7 Hz, 1H), 7.33 (d, J=2.7 Hz, 1H), 7.59 (s, 1H), 8.16 (s, 1H), 8.39 (d, J=9.0 Hz, 1H), 8.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 473 (M⁺+1)

Example 342 Cycloheptyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cycloheptanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 72%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.49-1.77 (m, 10H), 1.97-2.04 (m, 2H), 4.12 (s, 3H), 4.19 (s, 3H), 4.92-4.99 (m, 1H), 6.74 (s, 1H), 7.19 (d, J=9.0 Hz, 2H), 7.57 (d, J=9.0 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.79 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 439 (M⁺+1)

Example 343 Cycloheptyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cycloheptanol (26 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 73%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.42-1.79 (m, 10H), 1.80-2.04 (m, 2H), 4.12 (s, 3H), 4.20 (s, 3H), 4.95-4.99 (m, 1H), 7.14-7.20 (m, 2H), 7.32 (d, J=2.7 Hz, 1H), 7.59 (s, 1H), 8.16 (s, 1H), 8.40 (d, J=8.8 Hz, 1H), 8.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 473 (M⁺+1)

Example 344 Butyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-butanol (19 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (46 mg, yield 58%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.97 (t, J=7.3 Hz, 3H), 1.40-1.51 (m, 2H), 1.60-1.72 (m, 2H), 4.12 (s, 3H), 4.19 (s, 3H), 4.19 (t, J=6.6 Hz, 2H), 6.77 (s, 1H), 7.20 (d, J=9.0 Hz, 2H), 7.58 (d, J=8.8 Hz, 2H), 7.62 (s, 1H), 8.14 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 398 (M⁺+1)

Example 345 Butyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-butanol (17 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (50 mg, yield 66%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.98 (t, J=7.3 Hz, 3H), 1.40-1.51 (m, 2H), 1.58-1.74 (m, 2H), 4.12 (s, 3H), 4.20 (s, 3H), 4.23 (t, J=6.6 Hz, 2H), 7.19-7.25 (m, 2H), 7.33 (d, J=2.7 Hz, 1H), 7.59 (s, 1H), 8.15 (s, 1H), 8.39 (d, J=8.8 Hz, 1H), 8.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 433 (M⁺+1)

Example 346 1-Phenylpropyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-phenyl-1-propanol (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (43 mg, yield 51%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.3 Hz, 3H), 1.86-1.95 (m, 1H), 2.00-2.08 (m, 1H), 4.11 (s, 3H), 4.19 (s, 3H), 5.68 (t, J=7.3 Hz, 1H), 7.15-7.17 (m, 1H), 7.25-7.38 (m, 5H), 7.39 (d, J=4.6 Hz, 2H), 7.57 (s, 1H), 8.15 (s, 1H), 8.37 (d, J=9.3 Hz, 1H), 8.81 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 495 (M⁺+1)

Example 347 Isopropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-propanol (14 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (50 mg, yield 75%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.34 (d, J=6.3 Hz, 6H), 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.04-5.07 (m, 1H), 6.38 (s, 1H), 6.58 (brs, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.95 (s, 1H), 8.15 (s, 1H), 8.46 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 412 (M⁺+1)

Example 348 Cycloheptylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cycloheptylmethanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (64 mg, yield 77%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.23-1.31 (m, 2H), 1.45-1.60 (m, 6H), 1.70-1.89 (m, 5H), 4.01 (d, J=6.8 Hz, 2H), 4.10 (s, 3H), 4.17 (s, 3H), 6.70 (d, J=6.3 Hz, 1H), 6.80 (s, 1H), 7.18 (d, J=9.0 Hz, 2H), 7.61 (d, J=8.8 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.48 (t, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 452 (M⁺+1)

Example 349 Cycloheptylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cycloheptylmethanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (64 mg, yield 83%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.23-1.31 (m, 2H), 1.47-1.59 (m, 6H), 1.70-1.90 (m, 5H), 2.13 (s, 3H), 2.29 (s, 3H), 4.01 (d, J=6.8 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 6.43 (s, 1H), 6.58 (d, J=6.3 Hz, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.92 (brs, 1H), 8.15 (s, 1H), 8.48 (t, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 350 Cycloheptylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cycloheptylmethanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.19-1.31 (m, 2H), 1.40-1.90 (m, 11H), 2.10 (s, 3H), 2.28 (s, 3H), 4.01 (d, J=6.8 Hz, 2H), 4.12 (s, 3H), 4.17 (s, 3H), 6.47 (s, 1H), 6.57 (d, J=6.1 Hz, 1H), 7.02 (d, J=9.0 Hz, 1H), 7.67 (s, 1H), 7.74 (brs, 1H), 8.14 (s, 1H), 8.50 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 351 Cycloheptylmethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cycloheptylmethanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (41 mg, yield 46%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.22-1.30 (m, 2H), 1.46-1.88 (m, 11H), 4.00 (d, J=6.8 Hz, 2H), 4.12 (s, 3H), 4.19 (s, 3H), 6.78 (s, 1H), 7.20 (d, J=8.8 Hz, 2H), 7.58 (d, J=9.0 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.79 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 453 (M⁺+1)

Example 352 Cycloheptylmethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cycloheptylmethanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (53 mg, yield 63%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.23-1.31 (m, 2H), 1.47-1.91 (m, 11H), 4.02 (d, J=6.8 Hz, 2H), 4.12 (s, 3H), 4.20 (s, 3H), 7.19 (s, 1H), 7.21 (d, J=2.7 Hz, 1H), 7.33 (d, J=2.7 Hz, 1H), 7.59 (s, 1H), 8.15 (s, 1H), 8.39 (d, J=9.0 Hz, 1H), 8.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 487 (M⁺+1)

Example 353 2-Cyclohexylethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-cyclohexyl-1-ethanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (63 mg, yield 76%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.95-1.01 (m, 2H), 1.15-1.27 (m, 3H), 1.40-1.43 (m, 1H), 1.57-1.77 (m, 7H), 4.10 (s, 3H), 4.17 (s, 3H), 4.24 (t, J=6.8 Hz, 2H), 6.70 (d, J=6.3 Hz, 1H), 6.82 (s, 1H), 7.18 (d, J=8.8 Hz, 2H), 7.61 (d, J=8.8 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.48 (t, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 452 (M⁺+1)

Example 354 2-Cyclohexylethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-cyclohexyl-1-ethanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 88%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.94-1.02 (m, 2H), 1.16-1.28 (m, 3H), 1.40-1.44 (m, 1H), 1.58-1.78 (m, 7H), 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.25 (t, J=6.8 Hz, 2H), 6.42 (s, 1H), 6.59 (d, J=6.6 Hz, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.91 (s, 1H), 8.15 (s, 1H), 8.49 (t, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 355 2-Cyclohexylethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-cyclohexyl-1-ethanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (65 mg, yield 84%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.93-1.01 (m, 2H), 1.16-1.24 (m, 3H), 1.27-1.42 (m, 1H), 1.51-1.77 (m, 7H), 2.10 (s, 3H), 2.28 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.24 (t, J=6.8 Hz, 2H), 6.45 (s, 1H), 6.56 (d, J=6.6 Hz, 1H), 7.02 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 7.74 (brs, 1H), 8.15 (s, 1H), 8.49 (t, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 356 2-Cyclohexylethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-cyclohexyl-1-ethanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 54%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.95-1.01 (m, 2H), 1.15-1.27 (m, 3H), 1.41-1.77 (m, 8H), 4.12 (s, 3H), 4.19 (s, 3H), 4.23 (t, J=6.8 Hz, 2H), 6.76 (s, 1H), 7.20 (d, J=9.0 Hz, 1H), 7.58 (d, J=8.5 Hz, 1H), 7.62 (s, 1H), 8.15 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 453 (M⁺+1)

Example 357 2-Cyclohexylethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-cyclohexyl-1-ethanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (56 mg, yield 67%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96-1.02 (m, 2H), 1.16-1.28 (m, 3H), 1.42-1.78 (m, 8H), 4.12 (s, 3H), 4.20 (s, 3H), 4.26 (t, J=6.8 Hz, 2H), 7.18 (s, 1H), 7.20 (d, J=2.7 Hz, 1H), 7.33 (d, J=2.7 Hz, 1H), 7.59 (s, 1H), 8.16 (s, 1H), 8.39 (d, J=9.0 Hz, 1H), 8.83 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 487 (M⁺+1)

Example 358 1-Ethylpropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-pentanol (23 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (40 mg, yield 53%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.6 Hz, 6H), 1.62-1.71 (m, 4H), 4.10 (s, 3H), 4.17 (s, 3H), 4.75-4.79 (m, 1H), 6.70 (d, J=6.6 Hz, 1H), 6.80 (s, 1H), 7.18 (d, J=8.8 Hz, 2H), 7.62 (d, J=9.0 Hz, 2H), 7.64 (s, 1H), 8.14 (s, 1H), 8.49 (t, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 412 (M⁺+1)

Example 359 1-Ethylpropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-pentanol (20 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (53 mg, yield 74%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.97 (t, J=7.6 Hz, 6H), 1.59-1.70 (m, 4H), 2.13 (s, 3H), 2.30 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.76-4.79 (m, 1H), 6.43 (s, 1H), 6.58 (d, J=6.3 Hz, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.96 (s, 1H), 8.14 (s, 1H), 8.46 (t, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 440 (M⁺+1)

Example 360 1-Ethylpropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-pentanol (20 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 87%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.97 (t, J=7.6 Hz, 6H), 1.59-1.70 (m, 4H), 2.10 (s, 3H), 2.28 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 4.76-4.79 (m, 1H), 6.44 (s, 1H), 6.56 (d, J=6.3 Hz, 1H), 7.02 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 7.78 (brs, 1H), 8.15 (s, 1H), 8.46 (t, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 440 (M⁺+1)

Example 361 1-Ethylpropyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-pentanol (23 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (55 mg, yield 67%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.95 (t, J=7.6 Hz, 6H), 1.59-1.69 (m, 4H), 4.13 (s, 3H), 4.19 (s, 3H), 4.75-4.78 (m, 1H), 6.75 (s, 1H), 7.19 (d, J=9.0 Hz, 2H), 7.59 (d, J=9.0 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 413 (M⁺+1)

Example 362 1-Ethylpropyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-pentanol (20 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (49 mg, yield 63%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.97 (t, J=7.6 Hz, 6H), 1.58-1.69 (m, 4H), 4.12 (s, 3H), 4.20 (s, 3H), 4.77-4.80 (m, 1H), 7.18 (s, 1H), 7.33 (d, J=2.4 Hz, 1H), 7.59 (s, 1H), 8.16 (s, 1H), 8.42 (d, J=9.0 Hz, 1H), 8.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 447 (M⁺+1)

Example 363 Cyclopentyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclopentanol (22 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (40 mg, yield 53%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.60-1.94 (m, 8H), 4.10 (s, 3H), 4.17 (s, 3H), 5.23-5.24 (m, 1H), 6.69 (d, J=6.3 Hz, 1H), 6.74 (s, 1H), 7.17 (d, J=9.0 Hz, 2H), 7.60 (d, J=9.0 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.48 (t, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 410 (M⁺+1)

Example 364 Cyclopentyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclopentanol (20 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (70 mg, yield 99%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.58-1.96 (m, 8H), 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.22-5.23 (m, 1H), 6.38 (s, 1H), 6.58 (d, J=6.6 Hz, 1H), 6.94 (s, 1H), 7.65 (s, 1H), 7.95 (s, 1H), 8.15 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 438 (M⁺+1)

Example 365 Cyclopentyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclopentanol (20 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 84%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.66-1.95 (m, 8H), 2.10 (s, 3H), 2.27 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.21-5.25 (m, 1H), 6.41 (s, 1H), 6.56 (d, J=6.3 Hz, 1H), 7.01 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 7.78 (d, J=8.8 Hz, 1H), 8.15 (s, 1H), 8.47 (t, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 438 (M⁺+1)

Example 366 Cyclopentyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclopentanol (22 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 76%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.49-1.93 (m, 8H), 4.12 (s, 3H), 4.19 (s, 3H), 5.22-5.23 (m, 1H), 6.71 (s, 1H), 7.19 (d, J=9.0 Hz, 2H), 7.57 (d, J=8.8 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 410 (M⁺+1)

Example 367 Cyclopentyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then dded thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclopentanol (20 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.49-1.99 (m, 8H), 4.12 (s, 3H), 4.20 (s, 3H), 5.23-5.27 (m, 1H), 7.13 (s, 1H), 7.19 (dd, J=2.9, 9.0 Hz, 1H), 7.32 (d, J=2.7 Hz, 1H), 7.59 (s, 1H), 8.16 (s, 1H), 8.40 (d, J=9.0 Hz, 1H), 8.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 368 1-Butylpentyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 5-nonanol (38 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (2 mg, yield 2%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.92 (t, J=7.1 Hz, 6H), 1.31-1.39 (m, 8H), 1.57-1.64 (m, 4H), 4.11 (s, 3H), 4.17 (s, 3H), 4.85-4.91 (m, 1H), 6.69 (d, J=6.8 Hz, 1H), 7.18 (d, J=9.0 Hz, 2H), 7.61 (d, J=8.8 Hz, 2H), 7.64 (s, 1H), 8.15 (d, J=3.9 Hz, 1H), 8.4.6 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 369 1-Butylpentyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 5-nonanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (56 mg, yield 70%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.93 (t, J=7.1 Hz, 6H), 1.37-1.39 (m, 8H), 1.61 (brs, 1H), 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.87-4.90 (m, 1H), 6.41 (s, 1H), 6.58 (d, J=6.6 Hz, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.97 (s, 1H), 8.15 (d, J=3.9 Hz, 1H), 8.46 (t, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 370 1-Butylpentyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 5-nonanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (57 mg, yield 72%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.92 (t, J=7.1 Hz, 6H), 1.36 (brs, 8H), 1.56-1.60 (m, 4H), 2.10 (s, 3H), 2.28 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 4.87-4.90 (m, 1H), 6.42 (s, 1H), 6.55 (d, J=6.1 Hz, 1H), 7.02 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 7.80 (brs, 1H), 8.16 (d, J=3.9 Hz, 1H), 8.45 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 371 1-Butylpentyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 5-nonanol (38 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (40 mg, yield 44%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.90-0.93 (m, 6H), 1.34-1.35 (m, 8H), 1.59 (brs, 4H), 4.13 (s, 3H), 4.19 (s, 3H), 4.86-4.89 (m, 1H), 6.71 (s, 1H), 7.19 (d, J=9.0 Hz, 2H), 7.59 (d, J=8.8 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 469 (M⁺+1)

Example 372 1-Butylpentyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 5-nonanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (42 mg, yield 49%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.92 (t, J=7.1 Hz, 6H), 1.36 (brs, 8H), 1.61 (brs, 4H), 4.13 (s, 3H), 4.20 (s, 3H), 4.88-4.91 (m, 1H), 7.17 (s, 1H), 7.20 (s, 1H), 7.33 (s, 1H), 7.59 (s, 1H), 8.17 (s, 1H), 8.43 (d, J=9.0 Hz, 1H), 8.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 503 (M⁺+1)

Example 373 Allyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-propen-1-ol (13 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (56 mg, yield 84%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.71 (d, J=5.9 Hz, 2H), 5.32 (dd, J=1.2, 10.5 Hz, 1H), 5.40 (dd, J=1.5, 17.3 Hz, 1H), 5.96-6.06 (m, 1H), 6.49 (s, 1H), 6.59 (d, J=6.6 Hz, 1H), 6.96 (s, 1H), 7.65 (s, 1H), 7.91 (s, 1H), 8.16 (d, J=3.9 Hz, 1H), 8.49 (t, J=7.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 410 (M⁺+1)

Example 374 Allyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-propen-1-ol (13 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (50 mg, yield 75%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 2.28 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 4.71 (d, J=5.9 Hz, 2H), 5.31 (d, J=10.2 Hz, 1H), 5.40 (d, J=17.3 Hz, 1H), 5.96-6.04 (m, 1H), 6.50 (s, 1H), 6.56 (d, J=6.1 Hz, 1H), 7.03 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 7.76 (s, 1H), 8.16 (d, J=3.9 Hz, 1H), 8.48 (t, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 410 (M⁺+1)

Example 375 Allyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-propen-1-ol (15 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (42 mg, yield 54%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.13 (s, 3H), 4.19 (s, 3H), 4.70 (d, J=5.9 Hz, 2H), 5.29 (dd, J=1.2, 10.5 Hz, 1H), 5.39 (dd, J=1.5, 17.3 Hz, 1H), 5.93-6.03 (m, 1H), 6.81-6.87 (m, 1H), 7.20 (d, J=9.0 Hz, 2H), 7.59 (d, J=8.8 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 382 (M⁺+1)

Example 376 3-Phenylpropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-phenyl-1-propanol (35 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (54 mg, yield 64%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.01-2.08 (m, 2H), 2.75 (t, J=8.1 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), −4.24 (t, J=6.6 Hz, 2H), 6.70 (d, J=6.3 Hz, 1H), 6.80 (s, 1H), 7.17-7.33 (m, 7H), 7.61 (d, J=8.8 Hz, 2H), 7.64 (s, 1H), 8.15 (d, J=3.7 Hz, 1H), 8.50 (t, J=6.8 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 460 (M⁺+1)

Example 377 3-Phenylpropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-phenyl-1-propanol (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 98%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.02-2.09 (m, 2H), 2.13 (s, 3H), 2.29 (s, 3H), 2.76 (t, J=7.8 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 4.25 (t, J=6.6 Hz, 2H), 6.41 (s, 1H), 6.59 (d, J=6.3 Hz, 1H), 6.95 (s, 1H), 7.22-7.33 (m, 5H), 7.65 (s, 1H), 7.91 (s, 1H), 8.15 (d, J=3.7 Hz, 1H), 8.49 (t, J=6.8 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 378 3-Phenylpropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-phenyl-1-propanol (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (56 mg, yield 71%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.01-2.09 (m, 2H), 2.11 (s, 3H), 2.28 (s, 3H), 2.75 (t, J=8.1 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 4.24 (t, J=6.6 Hz, 2H), 6.43 (s, 1H), 6.56 (d, J=6.6 Hz, 1H), 7.03 (d, J=8.8 Hz, 1H), 7.21-7.33 (m, 5H), 7.67 (s, 1H), 7.75 (brs, 1H), 8.16 (d, J=3.9 Hz, 1H), 8.49 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 379 3-Phenylpropyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-phenyl-1-propanol (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (42 mg, yield 49%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.04-2.08 (m, 2H), 2.76 (t, J=8.3 Hz, 2H), 4.12 (s, 3H), 4.20 (s, 3H), 4.26 (t, J=6.6 Hz, 2H), 7.18-7.34 (m, 8H), 7.59 (s, 1H), 8.17 (s, 1H), 8.38 (d, J=8.8 Hz, 1H), 8.83 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 495 (M⁺+1)

Example 380 Cyclopropylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclopropylmethanol (19 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (25 mg, yield 34%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.33-0.37 (m, 2H), 0.60-0.65 (m, 2H), 1.18-1.22 (m, 1H), 4.04 (d, J=7.3 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 6.71 (s, 1H), 6.85 (s, 1H), 7.18 (d, J=8.5 Hz, 2H), 7.61 (d, J=8.3 Hz, 2H), 7.65 (s, 1H), 8.14 (s, 3H), 8.51 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 395 (M⁺+1)

Example 381 Cyclopropylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclopropylmethanol (17 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (51 mg, yield 74%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.34-0.38 (m, 2H), 0.61-0.66 (m, 2H), 1.18-1.24 (m, 1H), 2.13 (s, 3H), 2.30 (s, 3H), 4.04 (d, J=7.3 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 6.47 (s, 1H), 6.59 (s, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.92 (s, 1H), 8.15 (s, 1H), 8.48 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 424 (M⁺+1)

Example 382 Cyclopropylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclopropylmethanol (17 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (55 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.34-0.38 (m, 2H), 0.61-0.66 (m, 2H), 1.19-1.23 (m, 1H), 2.11 (s, 3H), 2.28 (s, 3H), 4.04 (d, J=7.3 Hz, 2H), 4.12 (s, 3H), 4.17 (s, 3H), 6.50 (s, 1H), 6.56 (s, 1H), 7.03 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 7.78 (s, 1H), 8.15 (s, 1H), 8.48 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 424 (M⁺+1)

Example 383 Cyclopropylmethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclopropylmethanol (19 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 75%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.33-0.36 (m, 2H), 0.59-0.64 (m, 2H), 1.16-1.23 (m, 1H), 4.03 (d, J=7.6 Hz, 2H), 4.12 (s, 3H), 4.17 (s, 3H), 6.81 (s, 1H), 7.20 (d, J=9.0 Hz, 2H), 7.57 (d, J=8.5 Hz, 2H), 7.61 (s, 1H), 7.99 (s, 1H), 8.77 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 396 (M⁺+1)

Example 384 Cyclopropylmethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclopropylmethanol (17 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (49 mg, yield 65%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.34-0.38 (m, 2H), 0.62-0.66 (m, 2H), 1.20-1.24 (m, 1H), 4.06 (d, J=7.3 Hz, 2H), 4.12 (s, 3H), 4.20 (s, 3H), 7.19-7.21 (m, 2H), 7.33 (s, 1H), 7.59 (s, 1H), 8.17 (s, 1H), 8.40 (d, J=8.8 Hz, 1H), 8.83 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 431 (M⁺+1)

Example 385 Cyclobutylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclobutylmethanol (22 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 64%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.80-2.13 (m, 6H), 2.65-2.71 (m, 1H), 4.10 (s, 3H), 4.17 (s, 3H), 4.18 (d, J=6.8 Hz, 2H), 6.70 (s, 1H), 6.80 (s, 1H), 7.18 (d, J=8.8 Hz, 2H), 7.60 (d, J=8.5 Hz, 2H), 7.64 (s, 1H), 8.14 (s, 1H), 8.50 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 410 (M⁺+1)

Example 386 Cyclobutylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclobutylmethanol (20 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 86%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.81-1.99 (m, 4H), 2.05-2.20 (m, 2H), 2.13 (s, 3H), 2.29 (s, 3H), 2.66-2.73 (m, 1H), 4.11 (s, 3H), 4.17 (s, 3H), 4.19 (d, J=7.1 Hz, 2H), 6.43 (s, 1H), 6.60 (s, 1H), 7.95 (s, 1H), 7.65 (s, 1H), 7.91 (s, 1H), 8.15 (s, 1H), 8.49 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 438 (M⁺+1)

Example 387 Cyclobutylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclobutylmethanol (20 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (59 mg, yield 83%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.78-2.08 (m, 6H), 2.08 (s, 3H), 2.26 (s, 3H), 2.60-2.70 (m, 1H), 4.09 (s, 3H), 4.15 (s, 3H), 4.16 (d, J=6.8 Hz, 2H), 6.43 (s, 1H), 6.55 (s, 1H), 7.00 (d, J=8.5 Hz, 1H), 7.65 (s, 1H), 7.74 (brs, 1H), 8.13 (s, 1H), 8.47 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 438 (M⁺+1)

Example 388 Cyclobutylmethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclobutylmethanol (22 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (55 mg, yield 67%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.80-1.99 (m, 4H), 2.07-2.14 (m, 2H), 2.64-2.71 (m, 1H), 4.12 (s, 3H), 4.17 (d, J=6.8 Hz, 2H), 4.19 (s, 3H), 6.79 (s, 1H), 7.20 (d, J=8.8 Hz, 2H), 7.58 (d, J=8.3 Hz, 2H), 7.62 (s, 1H), 8.11 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 410 (M⁺+1)

Example 389 Cyclobutylmethyl N-[2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclobutylmethanol (20 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (46 mg, yield 59%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.81-2.01 (m, 4H), 2.09-2.17 (m, 2H), 2.66-2.74 (m, 1H), 4.12 (s, 3H), 4.20 (d, J=6.8 Hz, 2H), 4.20 (s, 3H), 7.19 (s, 1H), 7.21 (d, J=2.7 Hz, 1H), 7.33 (d, J=2.4 Hz, 1H), 7.59 (s, 1H), 8.17 (s, 1H), 8.39 (d, J=9.3 Hz, 1H), 8.83 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 390 Cyclohexyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclohexanol (23 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (58 mg, yield 74%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.29-1.58 (m, 6H), 1.74-1.81 (m, 2H), 1.95-2.00 (m, 2H), 2.12 (s, 3H), 2.29 (s, 3H), 4.13 (s, 3H), 4.20 (s, 3H), 4.76-4.77 (m, 1H), 6.38 (s, 1H), 6.95 (s, 1H), 7.62 (s, 1H), 7.93 (s, 1H), 8.16 (s, 1H), 8.79 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 453 (M⁺+1)

Example 391 Cyclohexyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclohexanol (23 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (50 mg, yield 64%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.21-1.57 (m, 6H), 1.73-1.79 (m, 2H), 1.94-2.00 (m, 2H), 2.08 (s, 3H), 2.27 (s, 3H), 4.14 (s, 3H), 4.20 (s, 3H), 4.70-4.80 (m, 1H), 6.40 (s, 1H), 7.01 (d, J=8.8 Hz, 1H), 7.65 (s, 1H), 7.78 (brs, 1H), 8.16 (s, 1H), 8.78 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 453 (M⁺+1)

Example 392 Cyclopentyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclopentanol (20 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (47 mg, yield 61%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.49-1.84 (m, 6H), 1.89-1.98 (m, 2H), 2.12 (s, 3H), 2.28 (s, 3H), 4.13 (s, 3H), 4.20 (s, 3H), 5.21-5.22 (m, 1H), 6.36 (s, 1H), 6.95 (s, 1H), 7.62 (s, 1H), 7.93 (s, 1H), 8.16 (s, 1H), 8.79 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 439 (M⁺+1)

Example 393 Cyclopentyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclopentanol (20 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (43 mg, yield 56%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.49-1.83 (m, 6H), 1.88-1.97 (m, 2H), 2.08 (s, 3H), 2.26 (s, 3H), 4.14 (s, 3H), 4.20 (s, 3H), 5.20-5.25 (m, 1H), 6.39 (s, 1H), 7.01 (d, J=8.8 Hz, 1H), 7.65 (s, 1H), 7.77 (brs, 1H), 8.16 (s, 1H), 8.78 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 439 (M⁺+1)

Example 394 Cyclopentylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclopentylmethanol (26 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (42 mg, yield 54%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.22-1.84 (m, 8H), 2.25-2.29 (m, 1H), 4.10-4.17 (m, 8H), 6.69 (d, J=6.1 Hz, 1H), 6.80 (s, 1H), 7.18 (d, J=9.0 Hz, 2H), 7.61 (d, J=8.5 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.47 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 424 (M⁺+1)

Example 395 Cyclopentylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclopentylmethanol (23 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 85%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.31-1.68 (m, 6H), 1.78-1.86 (m, 2H), 2.13 (s, 3H), 2.20-2.30 (m, 1H), 2.29 (s, 3H), 4.10 (d, J=6.3 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 6.42 (s, 1H), 6.58 (d, J=6.3 Hz, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.91 (s, 1H), 8.16 (s, 1H), 8.46 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 452 (M⁺+1)

Example 396 Cyclopentylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclopentylmethanol (23 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 66%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.27-1.35 (m, 2H), 1.55-1.67 (m, 4H), 1.76-1.84 (m, 2H), 2.10 (s, 3H), 2.26-2.30 (m, 1H), 2.28 (s, 3H), 4.09 (d, J=7.1 Hz, 2H), 4.12 (s, 3H), 4.18 (s, 3H), 6.44 (s, 1H), 6.56 (s, 1H), 7.03 (d, J=8.5 Hz, 1H), 7.67 (s, 1H), 7.76 (brs, 1H), 8.16 (s, 1H), 8.45 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 452 (M⁺+1)

Example 397 Cyclopentylmethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclopentylmethanol (26 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (64 mg, yield 75%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.30-1.33 (m, 2H), 1.59-1.65 (m, 4H), 1.76-1.83 (m, 2H), 4.09 (d, J=7.3 Hz, 2H), 4.12 (s, 3H), 4.19 (s, 3H), 6.76 (s, 1H), 7.20 (d, J=9.0 Hz, 2H), 7.58 (d, J=8.8 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 425 (M⁺+1)

Example 398 Cyclopentylmethyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclopentylmethanol (23 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (47 mg, yield 59%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.29-1.34 (m, 2H), 1.57-1.66 (m, 4H), 1.77-1.85 (m, 2H), 4.11 (d, J=7.1 Hz, 2H), 4.12 (s, 3H), 4.20 (s, 3H), 7.19 (s, 1H), 7.33 (d, J=2.7 Hz, 1H), 7.59 (s, 1H), 8.17 (s, 1H), 8.39 (d, J=9.0 Hz, 1H), 8.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 459 (M⁺+1)

Example 399 2-Morpholinoethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-morpholino-1-ethanol (34 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (54 mg, yield 60%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.94-3.04 (m, 2H), 3.30-3.36 (m, 2H), 3.58-3.63 (m, 2H), 4.01-4.07 (m, 2H), 4.12 (s, 3H), 4.19 (s, 3H), 4.53-4.59 (m, 4H), 7.19 (d, J=9.0 Hz, 2H), 7.62 (s, 1H), 7.67 (d, J=9.0 Hz, 2H), 8.14 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 456 (M⁺+1)

Example 400 1-Propylbutyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-heptanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (53 mg, yield 61%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.95 (t, J=7.3 Hz, 6H), 1.19-1.62 (m, 8H), 4.13 (s, 3H), 4.19 (s, 3H), 4.90-4.93 (m, 1H), 6.72 (s, 1H), 7.19 (d, J=9.0 Hz, 2H), 7.58 (d, J=8.8 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 441 (M⁺+1)

Example 401 1-Ethylpentyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-heptanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (63 mg, yield 72%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.92-0.97 (m, 6H) 1.34-1.67 (m, 8H), 4.13 (s, 3H), 4.19 (s, 3H), 4.81-4.84 (m, 1H), 6.72 (s, 1H), 7.19 (d, J=9.0 Hz, 2H), 7.58 (d, J=9.0 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 441 (M⁺+1)

Example 402 2-(Tert-butyl)phenyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-(tert-butyl)phenol (39 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (74 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.41 (s, 9H), 4.13 (s, 3H), 4.19 (s, 3H), 7.08-7.11 (m, 1H), 7.19-7.29 (m, 5H), 7.41-7.44 (m, 1H), 7.63 (s, 1H), 7.70 (d, J=8.5 Hz, 2H), 8.15 (s, 1H), 8.79 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 475 (M⁺+1)

Example 403 2-Methoxyphenyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-methoxyphenol (32 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (16 mg, yield 18%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.87 (s, 3H), 4.13 (s, 3H), 4.19 (s, 3H), 6.97-7.02 (m, 2H), 7.15-7.26 (m, 5H), 7.62 (s, 1H), 7.66 (d, J=8.8 Hz, 2H), 8.16 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 448 (M⁺+1)

Example 404 2-Methylallyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-methyl-2-propen-1-ol (19 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (38 mg, yield 52%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.82 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.63 (s, 2H), 4.99 (s, 1H), 5.06 (s, 1H), 6.70 (d, J=6.3 Hz, 1H), 6.87 (s, 1H), 7.19 (d, J=9.0 Hz, 2H), 7.62 (d, J=9.0 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.48 (t, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 395 (M⁺+1)

Example 405 2-Methylallyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-methyl-2-propen-1-ol (17 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (31 mg, yield 45%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.83 (s, 3H), 2.13 (s, 3H), 2.30 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.64 (s, 2H), 5.00 (s, 1H), 5.06 (s, 1H), 6.59 (s, 1H), 6.96 (s, 1H), 7.65 (s, 1H), 8.16 (s, 1H), 8.46 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 424 (M⁺+1)

Example 406 2-Methylallyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-methyl-2-propen-1-ol (17 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (40 mg, yield 58%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.83 (s, 3H), 2.11 (s, 3H), 2.29 (s, 3H), 4.12 (s, 3H), 4.1.7 (s, 3H), 4.63 (s, 2H), 5.00 (s, 1H), 5.06 (s, 1H), 6.56 (d, J=5.9 Hz, 1H), 7.03 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 8.16 (s, 1H), 8.46 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 424 (M⁺+1)

Example 407 2-Methylallyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-methyl-2-propen-1-ol (19 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (37 mg, yield 47%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.13 (s, 3H), 4.19 (s, 3H), 4.62 (s, 2H), 4.98 (s, 1H), 5.05 (s, 1H), 6.87 (s, 1H), 7.21 (d, J=9.0 Hz, 2H), 7.59 (d, J=9.0 Hz, 2H), 7.62 (s, 1H), 8.15 (s, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 396 (M⁺+1)

Example 408 1-Ethyl-3-butynyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 5-hexyn-3-ol (26 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (30 mg, yield 39%).

¹H-NMR (CDCl₃-d₁, 400 MHz): 1.01 (t, J=7.6 Hz, 3H) 1.79-1.83 (m, 2H), 2.04-2.05 (m, 1H), 2.57-2.61 (m, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 4.90-4.93 (m, 1H), 6.69 (d, J=6.1 Hz, 1H), 6.83 (s, 1H), 7.19 (d, J=9.0 Hz, 2H), 7.61 (d, J=8.8 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.47 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 422 (M⁺+1)

Example 409 1-Ethyl-3-butynyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 5-hexyn-3-ol (23 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (52 mg, yield 72%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.01 (t, J=7.6 Hz, 3H), 1.79-1.83 (m, 2H), 2.05 (s, 1H), 2.13 (s, 3H), 2.30 (s, 3H), 2.55-2.60 (m, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 4.92-4.93 (m, 1H), 6.48 (s, 1H), 6.59 (s, 1H), 6.96 (s, 1H), 7.65 (s, 1H), 7.93 (s, 1H), 8.15 (s, 1H), 8.47 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 450 (M⁺+1)

Example 410 1-Ethyl-3-butynyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 5-hexyn-3-ol (23 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (43 mg, yield 59%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.01 (t, J=7.6 Hz, 3H), 1.79-1.81 (m, 2H), 2.04-2.05 (m, 1H), 2.11 (s, 3H), 2.29 (s, 3H), 2.57-2.61 (m, 2H), 4.12 (s, 3H), 4.17 (s, 3H), 4.90-4.93 (m, 1H), 6.50 (s, 1H), 6.56 (d, J=6.3 Hz, 1H), 7.03 (d, J=9.0 Hz, 1H), 7.67 (s, 1H), 7.75 (s, 1H), 8.16 (s, 1H), 8.45 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 450 (M⁺+1)

Example 411 1-Methylhexyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-heptanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (25 mg, yield 31%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.91 (t, J=7.1 Hz, 3H), 1.26-1.32 (m, 11H), 4.11 (s, 3H), 4.17 (s, 3H), 4.92-4.96 (m, 1H), 6.70 (s, 1H), 6.72 (s, 1H), 7.18 (d, J=8.5 Hz, 2H), 7.61 (d, J=8.3 Hz, 2H), 7.64 (s, 1H), 8.15 (s, 1H), 8.46 (s, 1H)

Mass spectrometry value (ESI-MS, m/z) 440 (M⁺+1)

Example 412 1-Methylhexyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-heptanol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (54 mg, yield 72%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.91 (t, J=7.1 Hz, 3H), 1.31-1.32 (m, 11H), 2.13 (s, 3H), 2.29 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 4.93-4.95 (m, 1H), 6.39 (s, 1H), 6.58 (d, J=5.6 Hz, 1H), 6.95 (s, 1H), 7.65 (s, 1H), 7.96 (s, 1H), 8.15 (s, 1H), 8.45 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 413 1-Methylhexyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-heptanol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (49 mg, yield 65%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.91 (t, J 6.6 Hz, 3H), 1.30-1.32 (m, 11H), 2.12 (s, 3H), 2.29 (s, 3H), 4.12 (s, 3H), 4.18 (s, 3H), 4.93-4.94 (m, 1H), 6.41 (s, 1H), 7.03 (s, 1H), 7.67 (s, 1H), 7.79 (s, 1H), 8.15 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 414 3-Piperidinopropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-piperidino-1-propanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (90 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.26 (s, 4H), 1.87-1.96 (m, 2H), 2.13 (s, 3H), 2.29-2.42 (m, 2H), 2.33 (s, 3H), 2.64-2.73 (m, 2H), 3.11-3.16 (m, 2H), 3.61-3.63 (m, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 4.31 (t, J=5.6 Hz, 2H), 6.59 (d, J=6.6 Hz, 1H), 6.96 (s, 1H), 7.65 (s, 1H), 7.84 (s, 1H), 8.15 (s, 1H), 8.47 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 495 (M⁺+1)

Example 415 3-Piperidinopropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-piperidino-1-propanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 73%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.62 (brs, 8H), 2.01 (brs, 2H), 2.13 (s, 3H), 2.27 (s, 3H), 3.00 (brs, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 4.29 (t, J=5.9 Hz, 2H), 6.27 (d, J=5.1 Hz, 1H), 6.99 (d, J=8.8 Hz, 1H), 7.44 (s, 1H), 7.57 (s, 1H), 7.61 (s, 1H), 8.44 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 495 (M⁺+1)

Example 416 1,3-Dioxo-2,3-dihydro-1H-2-isoindolyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-hydroxy-1,3-isoindolinedione (42 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (11 mg, yield 12%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.12 (s, 3H), 4.18 (s, 3H), 6.83 (d, J=6.1 Hz, 1H), 7.39 (d, J=9.0 Hz, 2H), 7.66 (s, 1H), 7.72 (d, J=9.0 Hz, 2H), 7.85-7.87 (m, 2H), 8.00-8.02 (m, 3H), 8.19 (s, 1H), 8.52-8.53 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 486 (M⁺+1)

Example 417 (1,3-Dioxo-2,3-dihydro-1H-2-isoindolyl)methyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-(hydroxymethyl)-1,3-isoindolinedione (41 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 57%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13 (s, 3H), 2.25 (s, 3H), 3.10-3.11 (m, 1H), 4.10 (s, 3H), 4.17 (s, 3H), 5.87 (s, 1H), 6.50 (s, 1H), 6.55 (s, 1H), 6.94 (s, 1H), 7.64 (s, 1H), 7.81-7.83 (m, 2H), 7.96-7.98 (m, 2H), 8.15 (s, 1H), 8.46 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 418 (1,3-Dioxo-2,3-dihydro-1H-2-isoindolyl)methyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-(hydroxymethyl)-1,3-isoindolinedione (41 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (14 mg, yield 17%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.09 (s, 3H), 2.24 (s, 3H), 3.10-3.11 (m, 1H), 4.11 (s, 3H), 4.17 (s, 3H), 5.27 (s, 1H), 5.87 (s, 1H), 6.53 (s, 1H), 7.01-7.04 (m, 1H), 7.66-7.96 (m, 7H)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 419 2-(1,3-Dioxo-2,3-dihydro-1H-2-isoindolyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-(2-hydroxyethyl)-1,3-isoindolinedione (44 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (57 mg, yield 66%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 2.26 (s, 3H), 4.05 (t, J=5.1 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 4.46 (t, J=5.4 Hz, 2H), 6.42 (s, 1H), 6.59 (d, J=6.3 Hz, 1H), 6.94 (s, 1H), 7.64 (s, 1H), 7.75-7.77 (m, 3H), 7.87-7.89 (m, 2H), 8.15 (s, 1H), 8.47 (t, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 543 (M⁺+1)

Example 420 2-(1,3-Dioxo-2,3-dihydro-1H-2-isoindolyl)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-(2-hydroxyethyl)-1,3-isoindolinedione (44 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (21 mg, yield 24%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.08 (s, 3H), 2.24 (s, 3H), 4.05 (t, J=5.1 Hz, 2H), 4.11 (s, 3H), 4.17 (s, 3H), 4.46 (t, J=5.4 Hz, 2H), 6.45 (s, 1H), 6.55 (s, 1H), 6.99 (d, J=8.5 Hz, 1H), 7.66 (s, 2H), 7.74-7.76 (m, 2H), 7.86-7.88 (m, 2H), 8.16 (s, 1H), 8.46 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 543 (M⁺+1)

Example 421 3-Morpholinopropyl N-{4-1 (6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-morpholino-1-propanol (38 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (38 mg, yield 41%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.89-1.96 (m, 2H), 2.51-2.53 (m, 6H), 3.76 (t, J=4.9 Hz, 4H), 4.05 (s, 3H), 4.06 (s, 3H), 4.27 (t, J=6.6 Hz, 2H), 6.45 (d, J=5.4 Hz, 1H), 6.74 (s, 1H), 7.15 (d, J=9.0 Hz, 2H), 7.45 (s, 1H), 7.49 (d, J=8.8 Hz, 2H), 7.56 (s, 1H), 8.48 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 469 (M⁺+1)

Example 422 3-Morpholinopropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-morpholino-1-propanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (56 mg, yield 66%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.89-1.96 (m, 2H), 2.15 (s, 3H), 2.25 (s, 3H), 2.50 (brs, 6H), 3.75 (t, J=4.6 Hz, 4H), 4.057 (s, 3H), 4.063 (s, 3H), 4.27 (t, J=6.6 Hz, 2H), 6.30 (d, J=5.1 Hz, 1H), 6.38 (s, 1H), 6.93 (s, 1H), 7.45 (s, 1H), 7.59 (s, 1H), 7.77 (s, 1H), 8.45 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 423 3-Morpholinopropyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-morpholino-1-propanol (33 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (66 mg, yield 77%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 2.31 (s, 3H), 2.39 (brs, 2H), 2.93 (brs, 2H), 3.22 (brs, 2H), 3.53 (brs, 2H), 4.00-4.03 (m, 2H), 4.12 (s, 3H), 4.17 (s, 3H), 4.32 (brs, 4H), 6.57 (s, 1H), 7.01 (brs, 1H), 7.67 (s, 2H), 8.14 (s, 1H), 8.50 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 424 3-(4-Methylpiperazino)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-(4-methylpiperazino)-1-propanol (41 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (9 mg, yield 9%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.89-1.93 (m, 2H), 2.39 (s, 3H), 2.49-2.62 (m, 10H), 4.05 (s, 6H), 4.25 (t, J=6.3 Hz, 2H), 6.44 (d, J=5.4 Hz, 1H), 6.79 (s, 1H), 7.15 (d, J=8.8 Hz, 2H), 7.42 (s, 1H), 7.49 (d, J=8.5 Hz, 2H), 7.56 (s, 1H), 8.48 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 482 (M⁺+1)

Example 425 3-(4-Methylpiperazino)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-(4-methylpiperazino)-1-propanol (36 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (33 mg, yield 36%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.90-1.95 (m, 2H), 2.15 (s, 3H), 2.25 (s, 3H), 2.35 (s, 3H), 2.42-2.53 (m, 10H), 4.05 (s, 3H), 4.06 (s, 3H), 4.25 (t, J=6.3 Hz, 2H), 6.29 (d, J=5.4 Hz, 1H), 6.38 (s, 1H), 6.92 (s, 1H), 7.42 (s, 1H), 7.59 (s, 1H), 7.75 (s, 1H), 8.45 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 509 (M⁺+1)

Example 426 3-(Diethylamino)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-(diethylamino)-1-propanol (34 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (32 mg, yield 36%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.39 (t, J=7.1 Hz, 6H), 2.20-2.22 (m, 2H), 3.14-3.16 (m, 6H), 4.04 (s, 6H), 4.30 (t, J=5.6 Hz, 2H), 6.44 (d, J=5.1 Hz, 1H), 7.12 (d, J=8.8 Hz, 2H), 7.42 (s, 1H), 7.56 (s, 1H), 7.64 (d, J=8.1 Hz, 2H), 7.47 (d, J=5.1 Hz, 1H), 8.77 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 455 (M⁺+1)

Example 427 3-(Diethylamino)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-(diethylamino)-1-propanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (50 mg, yield 61%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.32 (t, J=7.1 Hz, 6H), 2.14 (s, 3H), 2.17-2.19 (m, 2H), 2.28 (s, 3H), 2.94-3.01 (m, 6H), 4.05 (s, 3H), 4.06 (s, 3H), 4.30 (t, J=5.9 Hz, 2H), 6.30 (d, J=5.4 Hz, 1H), 6.93 (s, 1H), 7.11 (s, 1H), 7.42 (s, 1H), 7.59 (s, 1H), 7.68 (s, 1H), 8.44 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 483 (M⁺+1)

Example 428 3-(Diethylamino)propyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-(diethylamino)-1-propanol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (65 mg, yield 78%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.47 (t, J=7.1 Hz, 6H), 2.09 (s, 3H), 2.30 (s, 2H), 2.33 (s, 3H), 3.24 (brs, 6H), 4.12 (s, 3H), 4.17 (s, 3H), 4.33 (s, 2H), 6.57 (s, 1H), 7.01 (d, J=8.5 Hz, 1H), 7.67 (s, 2H), 8.15 (s, 1H), 8.46 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 483 (M⁺+1)

Example 429 3-(Diethylamino)propyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-(diethylamino)-1-propanol (34 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (25 mg, yield 27%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.24-1.35 (m, 6H), 2.16-2.17 (m, 2H), 3.05 (brs, 6H), 4.07 (s, 6H), 4.28 (s, 2H), 7.19 (d, J=8.5 Hz, 2H), 7.31 (s, 1H), 7.55 (S, 1H), 7.60 (d, J=8.5 Hz, 2H), 8.22 (s, 1H), 8.60 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 456 (M⁺+1)

Example 430 2-Pyridylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-pyridylmethanol (25 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (75 mg, yield 94%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.12 (s, 3H), 2.50 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 5.70 (s, 2H), 6.60 (s, 1H), 6.97 (s, 1H), 7.66 (s, 1H), 7.84-7.96 (m, 4H), 8.15 (s, 1H), 8.48 (s, 2H), 9.02 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 461 (M⁺+1)

Example 431 2-Pyridylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-pyridylmethanol (25 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (50 mg, yield 63%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 2.47 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 5.70 (s, 2H), 6.59 (d, J=5.9 Hz, 1H), 7.00 (d, J=9.5 Hz, 1H), 7.68 (s, 2H), 7.75-7.97 (m, 3H), 8.15 (s, 1H), 8.48 (t, J=7.1 Hz, 2H), 9.02 (d, J=4.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 461 (M⁺+1)

Example 432 3-Pyridylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-pyridylmethanol (25 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.12 (s, 3H), 2.33 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 5.47 (s, 2H), 6.58 (d, J=6.8 Hz, 1H), 7.04 (d, J=8.8 Hz, 1H), 7.67 (s, 2H), 7.98-8.01 (m, 1H), 8.14 (s, 1H), 8.46 (d, J=8.1 Hz, 1H), 8.53 (s, 1H), 8.79 (d, J=5.4 Hz, 1H), 9.22 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 461 (M⁺+1)

Example 433 4-Pyridylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-pyridylmethanol (28 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (10 mg, yield 12%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.046 (s, 3H), 4.049 (s, 3H), 5.24 (s, 2H), 6.45 (d, J=5.4 Hz, 1H), 7.17 (d, J=8.8 Hz, 2H), 7.23 (s, 1H), 7.30 (d, J=5.4 Hz, 2H), 7.45 (s, 1H), 7.53 (d, J=8.3 Hz, 2H), 7.56 (s, 1H), 8.48 (d, J=5.4 Hz, 1H), 8.62 (d, J=5.4 Hz, 2H)

Mass spectrometry value (ESI-MS, m/z): 433 (M⁺+1)

Example 434 4-Pyridylmethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-pyridylmethanol (28 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (21 mg, yield 23%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.069 (s, 3H), 4.073 (s, 3H), 5.25 (s, 2H), 7.22-7.27 (m, 2H), 7.32 (d, J=5.9 Hz, 2H), 7.34 (s, 1H), 7.53 (d, J=8.8 Hz, 2H), 7.55 (s, 1H), 8.63 (d, J=6.3 Hz, 3H)

Mass spectrometry value (ESI-MS, m/z): 433 (M⁺+1)

Example 435 2-(Diethylamino)ethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-(diethylamino)-1-ethanol (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (53 mg, yield 61%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.08 (t, J=7.1 Hz, 6H), 2.65 (q, J=7.1 Hz, 4H), 2.79 (t, J=5.9 Hz, 2H), 4.04 (s, 3H), 4.05 (s, 3H), 4.28 (t, J=5.9 Hz, 2H), 6.44 (d, J=5.4 Hz, 1H), 7.13-7.15 (m, 2H), 7.25-7.28 (m, 1H), 7.42 (s, 1H), 7.50 (d, J=8.8 Hz, 2H), 7.56 (s, 1H), 8.48 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 441 (M⁺+1)

Example 436 2-(Diethylamino)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-(diethylamino)-1-ethanol (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (66 mg, yield 71%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.10 (t, J=7.1 Hz, 6H), 2.67 (q, J=7.1 Hz, 4H), 2.80 (t, J=5.9 Hz, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 4.28 (t, J=5.9 Hz, 2H), 7.10 (s, 1H), 7.19-7.21 (m, 2H), 7.32 (s, 1H), 7.51 (d, J=8.8 Hz, 2H), 7.55 (s, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 442 (M⁺+1)

Example 437 1-(2-Morpholinoethyl)butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-morpholino-3-hexanol (49 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 81%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.91-0.96 (m, 3H), 1.36-1.82 (m, 6H), 2.41-2.45 (m, 6H), 3.70-3.72 (m, 4H), 4.04 (s, 3H), 4.05 (s, 3H), 4.95-4.97 (m, 1H), 6.44 (d, J=5.1 Hz, 1H), 7.14 (d, J=8.8 Hz, 2H), 7.30 (s, 1H), 7.42 (s, 1H), 7.53 (d, J=8.5 Hz, 2H), 7.57 (s, 1H), 8.47 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 511 (M⁺+1)

Example 438 1-(2-Morpholinoethyl)butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 1.0 min. Next, 1-morpholino-3-hexanol (43 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (74 mg, yield 81%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.3 Hz, 3H), 1.39-1.48 (m, 2H), 1.55-1.67 (m, 2H), 1.79-1.88 (m, 2H), 2.15 (s, 3H), 2.26 (s, 3H), 2.44-2.47 (m, 6H), 3.69-3.74 (m, 4H), 4.05 (s, 3H), 4.06 (s, 3H), 4.93-5.00 (m, 1H), 6.29 (d, J=5.1 Hz, 1H), 6.51 (s, 1H), 6.93 (s, 1H), 7.29 (s, 1H), 7.42 (s, 1H), 7.60 (s, 1H), 7.79 (s, 1H), 8.44 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 539 (M⁺+1)

Example 439 1-(2-Morpholinoethyl)butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-morpholino-3-hexanol (43 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (82 mg, yield 90%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.3 Hz, 3H), 1.39-1.46 (m, 2H), 1.57-1.64 (m, 2H), 1.78-1.86 (m, 2H), 2.13 (s, 3H), 2.26 (s, 3H), 2.46 (s, 6H), 3.69-3.73 (m, 4H), 4.04 (s, 3H), 4.07 (s, 3H), 4.95-4.97 (m, 1H), 6.27 (d, J=5.4 Hz, 1H), 6.75 (s, 1H), 7.00 (d, J=8.5 Hz, 1H), 7.31 (s, 1H), 7.42 (s, 1H), 7.59 (s, 1H), 7.62 (s, 1H), 8.43 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 539 (M⁺+1)

Example 440 1-(2-Morpholinoethyl)butyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-morpholino-3-hexanol (49 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (77 mg, yield 73%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.84-0.88 (m, 3H), 1.28-1.75 (m, 6H), 2.34-2.37 (m, 6H), 3.63-3.65 (m, 4H), 3.98 (s, 3H), 3.99 (s, 3H), 4.86-4.87 (m, 1H), 7.00 (s, 1H), 7.12 (d, J=8.8 Hz, 2H), 7.24 (s, 1H), 7.43 (d, J=8.5 Hz, 2H), 7.48 (s, 1H), 8.54 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 512 (M⁺+1)

Example 441 1-[2-(Diethylamino)ethyl]butyl N-{4-(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-(diethylamino)-3-hexanol (45 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (10 mg, yield 10%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.6 Hz, 3H), 1.28 (t, J=7.6 Hz, 6H), 1.38-1.46 (m, 2H), 1.55-1.73 (m, 4H), 2.93-2.95 (m, 6H), 4.05 (s, 6H), 4.90-4.93 (m, 1H), 6.44 (d, J=5.4 Hz, 1H), 7.14 (d, J=9.0 Hz, 2H), 7.42 (s, 1H), 7.54 (d, J=9.0 Hz, 2H), 7.56 (s, 1H), 8.47 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 442 1-[2-(Diethylamino)ethyl]butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-(diethylamino)-3-hexanol (40 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (29 mg, yield 32%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.3 Hz, 3H), 1.20 (t, J=7.3 Hz, 6H), 1.37-1.49 (m, 2H), 1.55-1.71 (m, 2H), 1.93-1.98 (m, 2H), 2.15 (s, 3H), 2.26 (s, 3H), 2.76-2.80 (m, 6H), 4.05 (s, 3H), 4.06 (s, 3H), 4.89-4.96 (m, 1H), 6.29 (d, J=5.4 Hz, 1H), 6.59 (s, 1H), 6.93 (s, 1H), 7.42 (s, 1H), 7.59 (s, 1H), 7.76 (s, 1H), 8.44 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 443 1-[2-(Diethylamino)ethyl]butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-(diethylamino)-3-hexanol (40 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (30 mg, yield 34%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.3 Hz, 3H), 1.19 (t, J=6.6 Hz, 6H), 1.41-1.45 (m, 2H), 1.60-1.68 (m, 2H), 1.95 (brs, 2H), 2.12 (s, 3H), 2.26 (s, 3H), 2.78-2.80 (m, 6H), 4.05 (s, 3H), 4.07 (s, 3H), 4.92 (brs, 1H), 6.26 (d, J=5.1 Hz, 1H), 6.65 (s, 1H), 6.99 (d, J=8.5 Hz, 1H), 7.27 (s, 1H), 7.43 (s, 1H), 7.61 (s, 1H), 8.43 (d, J=4.9 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 444 1-[2-(Diethylamino)ethyl]butyl N-{4-(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-(diethylamino)-3-hexanol (45 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (5 mg, yield 5%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.93-1.02 (m, 3H), 1.26 (t, J=6.8 Hz, 6H), 1.37-1.45 (m, 2H), 1.54-2.03 (m, 4H), 2.90 (brs, 6H), 4.067 (s, 3H), 4.072 (s, 3H), 4.90-4.93 (m, 1H), 7.21 (d, J=8.8 Hz, 2H), 7.32 (s, 1H), 7.49-7.56 (m, 3H), 8.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 498 (M⁺+1)

Example 445 1-(2-Piperidinoethyl)butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-piperidino-3-hexanol (48 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (57 mg, yield 58%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.94 (t, J=7.3 Hz, 3H), 1.35-1.46 (m, 4H), 1.52-1.67 (m, 6H), 1.85-1.90 (m, 2H), 2.40-2.56 (m, 6H), 4.04 (s, 3H), 4.05 (s, 3H), 4.90-4.93 (m, 1H), 6.44 (d, J=5.4 Hz, 1H), 7.14 (d, J=8.8 Hz, 2H), 7.28 (s, 3H), 7.42 (s, 1H), 7.52 (d, J=8.8 Hz, 2H), 7.56 (s, 1H), 8.47 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 509 (M⁺+1)

Example 446 1-(2-Piperidinoethyl)butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-piperidino-3-hexanol (43 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (75 mg, yield 82%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.3 Hz, 3H), 1.38-1.46 (m, 4H), 1.57-1.67 (m, 6H), 1.84-1.89 (m, 2H), 2.15 (s, 3H), 2.25 (s, 3H), 2.43-2.47 (m, 6H), 4.05 (s, 3H), 4.06 (s, 3H), 4.89-4.95 (m, 1H), 6.29 (d, J=5.1 Hz, 1H), 6.49 (s, 1H), 6.92 (s, 1H), 7.42 (s, 1H), 7.60 (s, 1H), 7.78 (s, 1H), 8.44 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 537 (M⁺+1)

Example 447 1-(2-Piperidinoethyl)butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-piperidino-3-hexanol (43 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (76 mg, yield 83%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.95 (t, J=7.1 Hz, 3H), 1.46 (brs, 4H), 1.64 (brs, 6H), 1.87-1.88 (m, 2H), 2.04 (s, 3H), 2.12 (s, 3H), 2.26 (brs, 6H), 4.05 (s, 3H), 4.07 (s, 3H), 4.92 (brs, 1H), 6.26 (d, J=4.9 Hz, 1H), 6.68 (s, 1H), 6.99 (d, J=8.8 Hz, 1H), 7.42 (s, 1H), 7.62 (s, 2H), 8.43 (d, J=4.9 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 537 (M⁺+1)

Example 448 1-(2-Piperidinoethyl)butyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-piperidino-3-hexanol (48 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (75 mg, yield 71%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.86 (t, J=7.1 Hz, 3H), 1.30-1.33 (m, 4H), 1.39-1.57 (m, 6H), 1.77-1.80 (m, 2H), 2.34-2.41 (m, 6H), 3.99 (s, 3H), 4.00 (s, 3H), 4.82-4.83 (m, 1H), 7.12 (d, J=8.5 Hz, 2H), 7.21 (s, 1H), 7.25 (s, 1H), 7.44 (d, J=8.3 Hz, 2H), 7.48 (s, 1H), 8.54 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 510 (M⁺+1)

Example 449 1-[2-(4-Methylpiperazino)ethyl]butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-(4-methylpiperazino)-3-hexanol (52 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (37 mg, yield 35%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.95 (t, J=7.1 Hz, 3H), 1.37-1.44 (m, 2H), 1.56-1.65 (m, 2H), 1.78-1.83 (m, 2H), 2.30 (s, 3H), 2.44-2.48 (m, 10H), 4.047 (s, 3H), 4.050 (s, 3H), 4.93-4.94 (m, 1H), 6.43 (d, J=5.4 Hz, 1H), 6.97 (s, 1H), 7.14 (d, J=9.0 Hz, 2H), 7.42 (s, 1H), 7.50 (d, J=8.5 Hz, 2H), 7.56 (s, 1H), 8.47 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 524 (M⁺+1)

Example 450 1-[2-(4-Methylpiperazino)ethyl]butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-(4-methylpiperazino)-3-hexanol (46 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 49%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.3 Hz, 3H), 1.39-1.46 (m, 2H), 1.58-1.64 (m, 2H), 1.82-1.85 (m, 2H), 2.15 (s, 3H), 2.25 (s, 3H), 2.31 (s, 3H), 2.48-2.50 (m, 10H), 4.05 (s, 3H), 4.07 (s, 3H), 6.29 (d, J=5.1 Hz, 1H), 6.41 (s, 1H), 6.93 (s, 1H), 7.43 (s, 1H), 7.60 (s, 1H), 7.79 (s, 1H), 8.44 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 552 (M⁺+1)

Example 451 1-[2-(4-Methylpiperazino)ethyl]butyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-(4-methylpiperazino)-3-hexanol (46 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (25 mg, yield 25%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.3 Hz, 3H), 1.40-1.45 (m, 2H), 1.57-1.63 (m, 2H), 1.82-1.84 (m, 2H), 2.12 (s, 3H), 2.25 (s, 3H), 2.31 (s, 3H), 2.46-2.49 (m, 10H), 4.05 (s, 3H), 4.07 (s, 3H), 4.94 (brs, 1H), 6.25 (d, J=5.1 Hz, 1H), 6.45 (s, 1H), 6.99 (d, J=8.8 Hz, 1H), 7.43 (s, 1H), 7.62 (s, 2H), 8.43 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 552 (M⁺+1)

Example 452 1-[2-(4-Methylpiperazino)ethyl]butyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-(4-methylpiperazino)-3-hexanol (52 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (12 mg, yield 11%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.11 (t, J=7.1 Hz, 3H), 1.37-1.42 (m, 2H), 1.53-1.60 (m, 2H), 1.70-1.80 (m, 2H), 2.21 (s, 3H), 2.31-2.50 (m, 10H), 4.07 (s, 6H), 4.94 (brs, 1H), 6.78 (s, 1H), 7.20 (d, J=8.5 Hz, 1H), 7.32 (s, 1H), 7.50 (d, J=8.5 Hz, 2H), 7.56 (s, 1H), 8.61 (s, 2H)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 453 Cyano(phenyl)methyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-hydroxy-2-phenylacetonitrile (35 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (20 mg, yield 24%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.04 (s, 3H), 4.06 (s, 3H), 5.95 (s, 1H), 6.58 (d, J=5.1 Hz, 1H), 7.27 (s, 1H), 7.30 (d, J=9.0 Hz, 2H), 7.46-7.58 (m, 8H), 8.54 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 457 (M⁺+1)

Example 454 Cyano(phenyl)methyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-hydroxy-2-phenylacetonitrile (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (30 mg, yield 39%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.11-2.27 (m, 6H), 4.05 (s, 3H), 4.06 (s, 3H), 5.96-6.01 (m, 1H), 6.41-6.43 (m, 1H), 7.05-7.12 (m, 1H), 7.24-7.27 (m, 1H), 7.46-7.54 (m, 7H), 8.49-8.51 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 485 (M⁺+1)

Example 455 Cyano(phenyl)methyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-hydroxy-2-phenylacetonitrile (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (30 mg, yield 39%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10-2.26 (m, 6H), 4.06 (s, 6H), 5.98-6.02 (m, 1H), 6.36-6.38 (m, 1H), 7.08-7.12 (m, 1H), 7.20-7.27 (m, 1H), 7.46-7.57 (m, 7H), 8.47-8.49 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 485 (M⁺+1)

Example 456 2-Cyanophenyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-hydroxyphenyl cyanide (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (5 mg, yield 6%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.01 (s, 3H), 4.02 (s, 3H), 6.78-6.85 (m, 2H), 6.96-7.01 (m, 3H), 7.13-7.15 (m, 1H), 7.31-7.35 (m, 1H), 7.43-7.51 (m, 3H), 7.61 (s, 1H), 7.95 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 443 (M⁺+1)

Example 457 3-Cyanophenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-hydroxybenzonitrile (31 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (5 mg, yield 6%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.11 (s, 3H), 4.19 (s, 3H), 6.78 (d, J=5.6 Hz, 1H), 7.52-7.54 (m, 1H), 7.60 (s, 1H), 7.73-7.76 (m, 2H), 8.20 (s, 1H), 8.55 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 442 (M⁺+1)

Example 458 3-Cyanophenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-hydroxybenzonitrile (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (40 mg, yield 53%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.13-2.16 (m, 3H), 2.28-2.39 (m, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 6.59 (d, J=6.8 Hz, 1H), 7.03 (s, 1H), 7.15-7.19 (m, 2H), 7.52-7.57 (m, 3H), 7.65 (s, 1H), 8.12-8.13 (m, 1H), 8.45-8.47 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 471 (M⁺+1)

Example 459 3-Cyanophenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-hydroxybenzonitrile (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (40 mg, yield 53%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10-2.15 (m, 3H), 2.27-2.37 (m, 3H), 4.11 (s, 3H), 4.16 (s, 3H), 6.56 (d, J=6.6 Hz, 1H), 7.02-7.20 (m, 3H), 7.52-7.56 (m, 3H), 7.67 (s, 1H), 8.13-8.14 (m, 1H), 8.44-8.46 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 471 (M⁺+1)

Example 460 4-Cyanophenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-hydroxybenzonitrile (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (40 mg, yield 53%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.16 (s, 3H), 2.39 (s, 3H), 4.11 (s, 3H), 4.17 (s, 3H), 6.97 (d, J=8.3 Hz, 1H), 7.03 (s, 1H), 7.38 (d, J=8.1 Hz, 2H), 7.65 (s, 1H), 7.74 (d, J=8.3 Hz, 2H), 7.91 (brs, 1H), 8.15 (s, 1H), 8.49 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 471 (M⁺+1)

Example 461 4-Cyanophenyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-hydroxybenzonitrile (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (40 mg, yield 53%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10-2.14 (m, 3H), 2.27-2.37 (m, 3H), 4.11-4.17 (m, 6H), 6.56 (d, J=6.1 Hz, 1H), 7.00 (d, J=8.8 Hz, 2H), 7.38 (d, J=8.8 Hz, 1H), 7.49 (d, J=9.0 Hz, 2H), 7.67 (s, 1H), 7.73 (d, J=8.8 Hz, 1H), 8.10-8.11 (m, 1H), 8.45-8.47 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 471 (M⁺+1)

Example 462 1-Methyl-3-piperidyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-methyl-3-piperidinol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (23 mg, yield 27%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.69-1.88 (m, 6H), 2.37 (s, 3H), 2.54-2.57 (m, 1H), 2.72 (brs, 1H), 4.05 (s, 6H), 5.02 (s, 1H), 6.44 (d, J=5.1 Hz, 1H), 7.14 (d, J=8.8 Hz, 2H), 7.42 (s, 1H), 7.50 (d, J=8.8 Hz, 2H), 7.56 (s, 1H), 8.47 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 439 (M⁺+1)

Example 463 1-Methyl-3-piperidyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-methyl-3-piperidinol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (29 mg, yield 36%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.77 (brs, 2H), 1.97 (brs, 2H), 2.14 (s, 3H), 2.25 (s, 3H), 2.35 (s, 3H), 2.60-2.67 (m, 4H), 4.05 (s, 3H), 4.06 (s, 3H), 5.01 (d, J=4.1 Hz, 1H), 6.29 (d, J=5.1 Hz, 1H), 6.69 (s, 1H), 6.91 (s, 1H), 7.42 (s, 1H), 7.59 (s, 1H), 7.82 (s, 1H), 8.44 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 464 1-Methyl-3-piperidyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-methyl-3-piperidinol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (22 mg, yield 27%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.69-1.90 (m, 6H), 2.11 (s, 3H), 2.26 (s, 3H), 2.37 (s, 3H), 2.62 (brs, 2H), 4.05 (s, 3H), 4.07 (s, 3H), 5.01 (s, 1H), 6.26 (d, J=5.4 Hz, 1H), 6.99 (d, J=8.8 Hz, 1H), 7.43 (s, 1H), 7.62 (s, 2H), 8.43 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 465 1-Methyl-3-piperidyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-methyl-3-piperidinol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (26 mg, yield 28%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.69-1.96 (m, 6H), 2.37 (s, 3H), 2.57-2.70 (m, 2H), 4.066 (s, 3H), 4.071 (s, 3H), 5.01 (s, 1H), 7.20 (d, J=8.8 Hz, 2H), 7.32 (s, 1H), 7.51 (d, J=9.0 Hz, 2H), 7.56 (s, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 440 (M⁺+1)

Example 466 1-Methyl-4-piperidyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-methyl-4-piperidinol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (41 mg, yield 47%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.76-1.85 (m, 2H), 2.01-2.09 (m, 4H), 2.31 (s, 3H), 2.71 (brs, 2H), 4.05 (s, 6H), 4.82 (brs, 1H), 6.44 (d, J=5.1 Hz, 1H), 6.89 (s, 1H), 7.15 (d, J=8.8 Hz, 2H), 7.42 (s, 1H), 7.49 (d, J=8.8 Hz, 2H), 7.56 (s, 1H), 8.48 (d, J=5.1 Hz, 2H)

Mass spectrometry value (ESI-MS, m/z): 439 (M⁺+1)

Example 467 1-Methyl-4-piperidyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-methyl-4-piperidinol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (41 mg, yield 51%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.77-1.86 (m, 2H), 1.92 (brs, 2H), 2.03-2.05 (m, 2H), 2.16 (d, J=9.0 Hz, 3H), 2.26 (s, 3H), 2.32 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 4.80-4.82 (m, 1H), 6.29 (d, J=5.4 Hz, 1H), 6.40 (s, 1H), 6.92 (s, 1H), 7.42 (s, 1H), 7.59 (s, 1H), 7.77 (brs, 1H), 8.44 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 468 1-Methyl-4-piperidyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-methyl-4-piperidinol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (33 mg, yield 41%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.76-1.85 (m, 2H), 2.01 (brs, 4H), 2.12 (s, 3H), 2.26 (s, 3H), 2.31 (s, 3H), 2.72 (brs, 2H), 4.05 (s, 3H), 4.07 (s, 3H), 4.78-4.82 (m, 1H), 6.26 (d, J=5.4 Hz, 1H), 6.47 (s, 1H), 7.00 (d, J=8.8 Hz, 1H), 7.43 (s, 1H), 7.62 (s, 2H), 8.44 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 469 1-Methyl-4-piperidyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-methyl-4-piperidinol (30 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (33 mg, yield 37%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.78-1.85 (m, 4H), 2.01 (brs, 2H), 2.32 (s, 3H), 2.71 (brs, 2H), 4.067 (s, 3H), 4.071 (s, 3H), 4.81 (s, 1H), 6.74 (s, 1H), 7.21 (d, J=9.0 Hz, 2H), 7.32 (s, 1H), 7.49 (d, J=8.5 Hz, 2H), 7.55 (s, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 440 (M⁺+1)

Example 470 Tetrahydro-2H-4-pyranyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, tetrahydro-2H-4-pyranol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 83%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.73-1.78 (m, 2H), 2.01-2.03 (m, 2H), 3.55-3.61 (m, 2H), 3.94-3.98 (m, 2H), 4.055 (s, 3H), 4.060 (s, 3H), 4.90-5.05 (m, 1H), 6.46 (d, J=5.4 Hz, 1H), 6.67 (s, 1H), 7.16 (d, J=8.8 Hz, 2H), 7.50 (d, J=8.5 Hz, 2H), 7.56 (s, 1H), 8.48 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 426 (M⁺+1)

Example 471 Tetrahydro-2H-4-pyranyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, tetrahydro-2H-4-pyranol (24 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (57 mg, yield 84%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.75-1.79 (m, 2H), 1.98-2.10 (m, 2H), 2.15 (s, 3H), 2.27 (s, 3H), 3.55-3.61 (m, 2H), 3.96-3.99 (m, 2H), 4.07 (s, 6H), 4.90-5.00 (m, 1H), 6.31 (d, J=4.9 Hz, 1H), 6.37 (s, 1H), 6.93 (s, 1H), 7.49 (s, 1H), 7.60 (s, 1H), 7.78 (s, 1H), 8.45 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 454 (M⁺+1)

Example 472 Tetrahydro-2H-4-pyranyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, tetrahydro-2H-4-pyranol (24 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (23 mg, yield 34%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.72-1.81 (m, 2H), 2.01-2.06 (m, 2H), 2.13 (s, 3H), 2.26 (s, 3H), 3.55-3.60 (m, 2H), 3.94-3.99 (m, 2H), 4.071 (s, 3H), 4.073 (s, 3H), 4.95-5.00 (m, 1H), 6.30 (d, J=5.4 Hz, 1H), 6.40 (s, 1H), 7.01 (d, J=8.8 Hz, 1H), 7.52 (s, 1H), 7.62 (s, 1H), 8.44 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 454 (M⁺+1)

Example 473 Tetrahydro-2H-4-pyranyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, tetrahydro-2H-4-pyranol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (38 mg, yield 53%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.70-1.80 (m, 2H), 2.00-2.05 (m, 2H), 3.55-3.60 (m, 2H), 3.94-3.98 (m, 2H), 4.07 (s, 6H), 4.93-5.01 (m, 1H), 6.65 (s, 1H), 7.22 (d, J=8.8 Hz, 2H), 7.35 (s, 1H), 7.51 (d, J=10.5 Hz, 2H), 7.56 (s, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 426 (M⁺+1)

Example 474 Cyclohexyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (12 mg), and cyclohexyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate (70 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (43 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (70 mg, yield 99%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.23-1.92 (m, 10H), 3.26 (s, 3H), 4.07 (s, 3H), 4.08 (s, 3H), 4.73 (s, 1H), 7.21-7.23 (m, 1H), 7.27 (s, 1H), 7.34 (s, 1H), 7.41 (d, J=2.7 Hz, 1H), 7.52 (s, 1H), 8.65 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 473 (M⁺+1)

Example 475 Cyclohexyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-ethylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (11 mg), and cyclohexyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate (65 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of ethyl iodide (87 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 88%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.20 (t, J=6.8 Hz, 3H), 1.24-1.91 (m, 10H), 3.54-3.59 (m, 1H), 3.83-3.89 (m, 1H), 4.07 (s, 3H), 4.08 (s, 3H), 4.73 (brs, 1H), 7.21-7.24 (m, 2H), 7.34 (s, 1H), 7.43 (d, J=2.7 Hz, 1H), 7.52 (s, 1H), 8.65 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 487 (M⁺+1)

Example 476 Cyclohexyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (7 mg), and cyclohexyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate (35 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (47 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (30 mg, yield 83%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.26-1.83 (m, 10H), 3.35 (s, 3H), 4.07 (s, 6H), 4.75-4.79 (m, 1H), 7.24 (d, J=8.8 Hz, 2H), 7.34-7.35 (m, 3H), 7.56 (s, 1H), 8.65 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 439 (M⁺+1)

Example 477 Cyclohexyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-ethylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (7 mg), and cyclohexyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate (35 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of ethyl iodide (52 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (35 mg, yield 93%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.23 (t, J=7.1 Hz, 3H), 1.36-1.93 (m, 10H), 3.73-3.78 (m, 1H), 3.91-3.98 (m, 1H), 4.07 (s, 6H), 4.76 (s, 1H), 7.19-7.34 (m, 4H), 7.51 (d, J=11.0 Hz, 1H), 7.56 (s, 1H), 8.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 453 (M⁺+1)

Example 478 2-Methoxybenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (11 mg), and 2-methoxybenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate (66 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (77 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (50 mg, yield 75%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.29 (s, 3H), 3.87 (s, 3H), 4.065 (s, 3H), 4.07 (s, 3H), 4.69 (s, 2H), 6.83-6.96 (m, 4H), 7.20-7.50 (m, 5H), 8.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 511 (M⁺+1)

Example 479 2-Methylbenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (11 mg), and 2-methylbenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate (62 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (77 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (57 mg, yield 89%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.21 (s, 3H), 3.28 (s, 3H), 4.069 (s, 3H), 4.074 (s, 3H), 5.10-5.19 (m, 2H), 7.12-7.23 (m, 5H), 7.33-7.35 (m, 2H), 7.41 (d, J=2.4 Hz, 1H), 7.51 (s, 1H), 8.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 495 (M⁺+1)

Example 480 2-Chlorobenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (11 mg), and 2-chlorobenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate (65 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (77 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (57 mg, yield 85%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.30 (s, 3H), 4.07 (s, 3H), 4.08 (s, 3H), 5.20-5.27 (m, 2H), 7.20-7.27 (m, 4H), 7.34-7.44 (m, 4H), 7.51 (s, 1H), 8.65 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 515 (M⁺+1)

Example 481 1-Propylbutyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (11 mg), and 1-propylbutyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate (62 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (77 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (43 mg, yield 68%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.87 (t, J=7.1 Hz, 6H), 1.24-1.82 (s, 8H), 3.26 (s, 3H), 4.07 (s, 3H), 4.08 (s, 3H), 4.80-4.83 (m, 1H), 7.21-7.24 (m, 1H), 7.31 (s, 1H), 7.34 (s, 1H), 7.42 (s, 1H), 7.52 (s, 1H), 8.66 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 489 (M⁺+1)

Example 482 Cycloheptyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (11 mg), and cycloheptyl N-2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenylcarbamate (61 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (77 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 95%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.44-1.93 (m, 12H), 3.25 (s, 3H), 4.07 (s, 3H), 4.08 (s, 3H), 4.90 (brs, 1H), 7.20-7.23 (m, 1H), 7.33-7.34 (m, 2H), 7.41 (d, J=2.7 Hz, 1H), 7.52 (s, 1H), 8.65 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 487 (M⁺+1)

Example 483 Cycloheptylmethyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (27 mg), and cycloheptylmethyl N-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenylcarbamate (153 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (193 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (100 mg, yield 63%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.15-1.81 (m, 13H), 3.42 (d, J=6.6 Hz, 3H), 3.99 (d, J=6.6 Hz, 2H), 4.05 (s, 6H), 6.44 (d, J=5.4 Hz, 1H), 7.14 (d, J=9.0 Hz, 2H), 7.43 (s, 1H), 7.49 (d, J=8.5 Hz, 2H), 7.56 (s, 1H), 8.48 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 466 (M⁺+1)

Example 484 Cycloheptylmethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (27 mg), and cycloheptylmethyl. N-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenylcarbamate (154 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (193 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (90 mg, yield 57%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.10-1.81 (m, 13H), 3.35 (s, 3H), 3.94 (d, J=6.6 Hz, 2H), 4.07 (s, 6H), 7.23-7.26 (m, 3H), 7.34-7.35 (m, 2H), 7.56 (s, 1H), 8.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 485 2-Methoxybenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-ethylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (11 mg), and 2-methoxybenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate (66 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of ethyl iodide (84 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (63 mg, yield 93%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.22 (t, J=7.1 Hz, 3H), 3.55-3.60 (m, 1H), 3.76-3.94 (m, 1H), 3.87 (s, 3H), 4.067 (s, 3H), 4.074 (s, 3H), 5.19 (d, J=3.4 Hz, 2H), 6.81-7.09 (m, 4H), 7.21-7.40 (m, 3H), 7.43 (d, J=2.7 Hz, 1H), 7.51 (s, 1H), 8.65 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 486 2-Methylbenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-ethylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (11 mg), and 2-methylbenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate (62 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of ethyl iodide (84 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (53 mg, yield 79%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.20-1.23 (m, 3H), 2.21 (s, 3H), 3.56-3.59 (m, 1H), 3.90-3.92 (m, 1H), 4.069 (s, 3H), 4.073 (s, 3H), 5.13-5.18 (m, 1H), 7.12-7.36 (m, 7H), 7.43 (s, 1H), 7.51 (s, 1H), 8.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 509 (M⁺+1)

Example 487 2-Chlorobenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-ethylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (11 mg), and 2-chlorobenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate (65 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of ethyl iodide (84 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (68 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.23 (t, J=7.1 Hz, 3H), 3.54-3.63 (m, 1H), 3.88-3.97 (m, 1H), 4.07 (s, 3H), 4.08 (s, 3H), 5.23 (s, 2H), 7.19-7.36 (m, 7H), 7.45 (d, J=2.4 Hz, 1H), 7.51 (s, 1H), 8.65 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 488 1-Propylbutyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-ethylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (11 mg), and 1-propylbutyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate (62 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of ethyl iodide (84 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (49 mg, yield 75%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.85-0.88 (m, 3H), 0.93-0.97 (s, 3H), 1.18-1.70 (m, 11H), 3.47-3.53 (m, 1H), 3.88-3.91 (m, 1H), 4.07 (s, 3H), 4.08 (s, 3H), 4.78%-4.95 (m, 1H), 7.21-7.23 (m, 1H), 7.32-7.34 (m, 2H), 7.43 (s, 1H), 7.52 (s, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 503 (M⁺+1)

Example 489 Cycloheptyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-ethylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (11 mg), and cycloheptyl N-2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenylcarbamate (61 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of ethyl iodide (84 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (51 mg, yield 78%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.20 (t, J=7.1 Hz, 3H), 1.29-2.03 (m, 12H), 3.53-3.58 (m, 1H), 3.83-3.88 (m, 1H), 4.07 (s, 3H), 4.08 (s, 3H), 4.89-4.98 (m, 1H), 7.21-7.23 (m, 1H), 7.27-7.34 (m, 2H), 7.43 (d, J=2.7 Hz, 1H), 7.52 (s, 1H), 8.65 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 501 (M⁺+1)

Example 490 2-Methoxybenzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (24 mg), and 2-methoxybenzyl N-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenylcarbamate (145 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (170 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (115 mg, yield 81%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.38 (s, 3H), 3.84 (s, 3H), 4.06 (s, 6H), 5.24 (s, 2H), 6.86-6.93 (m, 3H), 7.23-7.28 (m, 3H), 7.33 (s, 1H), 7.38 (d, J=8.8 Hz, 2H), 7.54 (s, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 477 (M⁺+1)

Example 491 2-Methylbenzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (24 mg), and 2-methylbenzyl N-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenylcarbamate (148 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (170 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (115 mg, yield 83%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.32 (s, 3H), 3.37 (s, 3H), 4.07 (s, 6H), 5.20 (s, 2H), 7.16-7.27 (m, 6H), 7.33 (s, 1H), 7.36 (d, J=6.6 Hz, 2H), 7.55 (s, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 461 (M⁺+1)

Example 492 2-Chlorobenzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (16 mg), and 2-chlorobenzyl N-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenylcarbamate (107 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (114 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (75 mg, yield 78%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.39 (s, 3H), 4.07 (s, 6H), 5.29 (s, 2H), 7.24-7.41 (m, 9H), 7.55 (s, 1H), 8.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 493 1-Propylbutyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (16 mg), and 1-propylbutyl N-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenylcarbamate (99 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (114 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (84 mg, yield 93%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.92 (t, J=7.3 Hz, 6H), 1.18-1.42 (m, 4H), 1.45-1.55 (m, 4H), 3.35 (s, 3H), 4.07 (s, 6H), 4.83-4.89 (m, 1H), 7.25 (d, J=8.8 Hz, 2H), 7.33 (s, 1H), 7.36 (d, J=8.5 Hz, 2H), 7.55 (s, 1H), 8.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 455 (M⁺+1)

Example 494 Cycloheptyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (24 mg), and cycloheptyl N-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenylcarbamate (144 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (170 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (117 mg, yield 86%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.26-1.93 (m, 12H), 3.34 (s, 3H), 4.07 (s, 6H), 4.91-4.95 (m, 1H), 7.24 (d, J=8.8 Hz, 2H), 7.33 (s, 1H), 7.36 (d, J=8.8 Hz, 2H), 7.55 (s, 1H), 8.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 453 (M⁺+1)

Example 495 1-Ethyl-3-butynyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (27 mg), and 1-ethyl-3-butynyl N-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenylcarbamate (143 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (193 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (83 mg, yield 56%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.84 (t, J=7.6 Hz, 3H), 1.64-1.65 (m, 2H), 1.93 (t, J=2.7 Hz, 2H), 2.44 (brs, 2H), 3.28 (s, 3H), 3.99 (s, 3H), 4.75-4.78 (m, 1H), 7.17 (d, J=8.8 Hz, 2H), 7.21 (s, 1H), 7.31 (d, J=8.8 Hz, 2H), 7.47 (s, 1H), 8.56 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 437 (M⁺+1)

Example 496 1-Ethyl-3-butynyl N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N-methylcarbamate

Dimethylformamide (5 ml) was added to sodium hydride (27 mg), and 1-ethyl-3-butynyl N-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenylcarbamate (143 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (193 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (24 mg, yield 16%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.85-0.87 (m, 3H), 1.67-1.75 (m, 2H), 1.918-1.924 (m, 1H), 2.46 (s, 2H), 3.29 (s, 3H), 3.97 (s, 3H), 3.98 (s, 3H), 4.76-4.79 (m, 1H), 6.44 (d, J=5.4 Hz, 1H), 7.09 (d, J=9.0 Hz, 2H), 7.30 (d, J=8.5 Hz, 2H), 7.36 (s, 1H), 7.47 (s, 1H), 8.43 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 436 (M⁺+1)

Example 497 Cyclohexyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-methoxyphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclohexanol (47 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (120 mg, yield 85%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.26-1.95 (m, 10H), 3.88 (s, 3H), 4.07 (s, 6H), 4.68-4.77 (m, 1H), 6.79-6.80 (m, 1H), 6.84-6.87 (m, 1H), 7.17 (s, 1H), 7.32 (s, 1H), 7.55 (s, 1H), 8.19 (s, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 455 (M⁺+1)

Example 498 Cycloheptyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-methoxyphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cycloheptanol (54 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (89 mg, yield 61%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.49-2.03 (m, 13H), 3.88 (s, 3H), 4.07 (s, 6H), 4.84-4.97 (m, 1H), 6.788-6.794 (m, 1H), 6.84-6.87 (m, 1H), 7.15 (s, 1H), 7.36 (s, 1H), 7.55 (s, 1H), 8.19 (s, 1H), 8.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 469 (M⁺+1)

Example 499 2-Chlorobenzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-methoxyphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-chlorophenyl)methanol (67 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (147 mg, yield 96%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.86 (s, 3H), 4.06 (s, 3H), 4.07 (s, 3H), 5.34 (s, 2H), 6.80-6.81 (m, 1H), 6.85-6.88 (m, 1H), 7.27-7.35 (m, 4H), 7.40-7.42 (m, 1H), 7.48-7.51 (m, 1H), 7.55 (s, 1H), 8.21 (s, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 500 2-Methoxybenzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-methoxyphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methoxyphenyl)methanol (58 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (148 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.86-3.91 (m, 8H), 4.06 (s, 3H), 4.07 (s, 3H), 6.84-7.32 (m, 6H), 7.33 (s, 1H), 7.55 (s, 1H), 8.23-8.30 (m, 1H), 8.65 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 493 (M⁺+1)

Example 501 2-(2-Pyridyl)ethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-methoxyphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 2-(2-pyridyl)-1-ethanol (58 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (110 mg, yield 75%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.20 (t, J=6.8 Hz, 2H), 3.85 (d, J=1.5 Hz, 3H), 4.07 (d, J=1.5 Hz, 6H), 4.60 (t, J=6.6 Hz, 2H), 6.78-6.89 (m, 1H), 6.84 (d, J=8.8 Hz, 1H), 7.16-7.27 (m, 3H), 7.32 (d, J=1.5 Hz, 1H), 7.54 (d, J=1.5 Hz, 1H), 7.62-7.66 (m, 1H), 8.18 (brs, 1H), 8.58 (d, J=4.9 Hz, 1H), 8.63 (d, J=1.7 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 478 (M⁺+1)

Example 502 1-Ethyl-3-butynyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-methoxyphenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 5-hexyn-3-ol (46 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (73 mg, yield 52%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.00 (t, J=7.3 Hz, 3H), 1.74-1.85 (m, 2H), 2.56-2.59 (m, 1H), 3.31-3.49 (m, 2H), 3.89 (s, 3H), 4.07 (s, 6H), 4.89-4.92 (m, 1H), 6.80 (d, J=2.4 Hz, 1H), 6.85-6.87 (m, 1H), 7.27 (s, 1H), 7.33 (s, 1H), 7.55 (s, 1H), 8.20 (brs, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 453 (M⁺+1)

Example 503 Cyclohexyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cyclohexanol (44 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (120 mg, yield 88%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.24-1.57 (m, 6H), 1.78-1.81 (m, 2H), 1.96-2.04 (m, 2H), 4.07 (s, 6H), 4.78-4.82 (m, 1H), 7.34 (s, 1H), 7.52 (s, 1H), 7.58-7.61 (m, 1H), 8.17 (d, J=2.9 Hz, 1H), 8.61 (s, 1H), 8.73 (d, J=9.3 Hz, 1H), 9.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 470 (M⁺+1)

Example 504 2-Chlorobenzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-chlorophenyl)methanol (63 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (74 mg, yield 50%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 4.08 (s, 6H), 5.39 (s, 2H), 7.26-7.33 (m, 2H), 7.37 (s, 1H), 7.43-7.45 (m, 1H), 7.49-7.52 (m, 2H), 7.59-7.62 (m, 1H), 8.18 (d, J=2.7 Hz, 1H), 8.61 (s, 1H), 8.74 (d, J=9.3 Hz, 1H), 9.97 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 512 (M⁺+1)

Example 505 2-Methylbenzyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methylphenyl)methanol (54 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (130 mg, yield 91%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.42 (s, 3H), 4.06 (s, 3H), 4.07 (s, 3H), 5.29 (s, 2H), 7.17-7.41 (m, 5H), 7.51 (s, 1H), 7.58-7.61 (m, 1H), 8.16 (d, J=2.9 Hz, 1H), 8.59 (s, 1H), 8.73 (d, J=9.3 Hz, 1H), 9.90 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 506 Cycloheptylmethyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cycloheptylmethanol (56 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (115 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.23-1.93 (m, 13H), 4.03 (d, J=6.8 Hz, 2H), 4.077 (s, 3H), 4.081 (s, 3H), 7.27 (s, 1H), 7.34 (s, 1H), 7.52 (s, 1H), 7.58-7.61 (m, 1H), 8.17 (d, J=2.7 Hz, 1H), 8.61 (s, 1H), 8.73 (d, J=9.3 Hz, 1H), 9.85 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 498 (M⁺+1)

Example 507 Cycloheptyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cycloheptanol (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (140 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.40-1.82 (m, 8H), 1.88-1.94 (m, 2H), 1.98-2.04 (m, 2H), 4.077 (s, 3H), 4.080 (s, 3H), 4.95-5.00 (m, 1H), 7.35 (s, 1H), 7.52 (s, 1H), 7.57-7.60 (m, 1H), 8.16 (d, J=2.7 Hz, 1H), 8.61 (s, 1H), 8.74 (d, J=9.3 Hz, 1H), 9.79 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 484 (M⁺+1)

Example 508 1-Butylpentyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 5-nonanol (64 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (143 mg, yield 96%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.89-0.94 (m, 6H), 1.33-1.65 (m, 12H), 4.077 (s, 3H), 4.083 (s, 3H), 4.89-4.92 (m, 1H), 7.35 (s, 1H), 7.52 (s, 1H), 7.57-7.60 (m, 1H), 8.17 (d, J=2.7 Hz, 1H), 8.60 (s, 1H), 8.76 (d, J=9.3 Hz, 1H), 9.83 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 514 (M⁺+1)

Example 509 Hexyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-hexanol (45 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (109 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.92 (t, J=7.1 Hz, 3H), 1.34-1.42 (m, 6H), 1.69-1.76 (m, 2H), 4.079 (s, 3H), 4.082 (s, 3H), 4.23 (t, J=6.8 Hz, 2H), 7.35 (s, 1H), 7.52 (s, 1H), 7.58-7.61 (m, 1H), 8.17 (d, J=2.9 Hz, 1H), 8.61 (s, 1H), 8.73 (d, J=9.3 Hz, 1H), 9.85 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 472 (M⁺+1)

Example 510 1-Ethyl-3-butynyl N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}carbamate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was added to toluene (10 ml) and triethylamine (1 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (140 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 5-hexyn-3-ol (43 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (115 mg, yield 85%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.01 (t, J=7.3 Hz, 3H), 1.77-1.87 (m, 2H), 2.04-2.05 (m, 1H), 2.58-2.60 (m, 2H), 4.079 (s, 3H), 4.083 (s, 3H), 4.91-4.96 (m, 1H), 7.35 (s, 1H), 7.52 (s, 1H), 7.59-7.62 (m, 1H), 8.18 (d, J=2.7 Hz, 1H), 8.61 (s, 1H), 8.73 (d, J=9.3 Hz, 1H), 9.87 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 511 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(2-diethylaminoethyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diethylphenylenediamine (50 mg) was added to thereto, and the mixture was further stirred at room temperature for 14 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (5 mg, yield 5%).

¹H-NMR (CDCl₃, 400 MHz): 0.89 (m, 6H), 2.15 (s, 3H), 2.28 (s, 3H), 2.46 (m, 4H), 2.62 (m, 2H), 3.67 (m, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 6.25 (m, 1H), 6.76 (br, 1H), 7.04 (d, J=8.5 Hz, 1H), 7.18 (d, J=8.6 Hz, 1H), 7.44 (s, 1H), 7.46 (br, 1H), 7.59 (s, 1H), 8.44 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 483 (M⁺+1)

Example 512 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(2-piperidinylethyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 3 hr. Next, 2-piperidinylethylamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (25 mg, yield 33%).

¹H-NMR (CDCl₃, 400 MHz): 1.35-1.46 (m, 6H), 2.17 (s, 3H), 2.29 (s, 3H), 2.32-2.56 (m, 6H), 3.69 (m, 2H), 4.06 (s, 6H), 6.29 (m, 1H), 6.78 (br, 1H), 7.05 (d, J=8.3 Hz, 1H), 7.19 (d, J=8.6 Hz, 1H), 7.48 (s, 1H), 7.50 (br, 1H), 7.59 (s, 1H), 8.45 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 513 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-[4-(N-benzyl)piperidinyl]thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 3 hr. Next, 4-amino-1-benzylpiperidine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (27 mg, yield 31%).

¹H-NMR (CDCl₃, 400 MHz): 1.38-2.26 (m, 10H), 2.80-2.88 (m, 4H), 3.53 (m, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 5.46 (br, 1H), 6.28 (d, J=5.4 Hz, 1H), 7.03 (d, J=8.3 Hz, 1H), 7.14 (d, J=8.5 Hz, 1H), 7.28-7.33 (m, 5H), 7.45 (s, 1H), 7.47 (br, 1H), 7.58 (s, 1H), 8.49 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 556 (M⁺+1)

Example 514 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-(2-piperidinylethyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (52 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 5 hr. Next, 2-piperidinylethylamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (32 mg, yield 40%).

¹H-NMR (CDCl₃, 400 MHz): 1.35-1.46 (m, 6H), 2.17 (s, 3H), 2.29 (s, 3H), 2.32-2.56 (m, 6H), 3.69 (m, 2H), 4.06 (s, 6H), 6.29 (m, 1H), 6.78 (br, 1H), 7.05 (d, J=8.3 Hz, 1H), 7.19 (d, J=8.6 Hz, 1H), 7.48 (s, 1H), 7.50 (br, 1H), 7.59 (s, 1H), 8.45 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 515 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-(2-acetamidoethyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (52 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 5 hr. Next, 2-acetamidoethylamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (6 mg, yield 8%).

¹H-NMR (CDCl₃, 400 MHz): 1.94 (s, 3H), 2.17 (s, 3H), 2.25 (s, 3H), 3.44 (m, 2H), 3.78 (m, 2H), 4.07 (s, 6H), 6.20 (m, 1H), 6.67 (br, 1H), 6.78 (br, 1H), 7.07 (s, 1H), 7.18 (s, 1H), 7.41 (br, 1H), 7.54 (s, 1H), 7.59 (s, 1H), 8.47 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 516 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-diethylaminoethyl)thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 5 hr. Next, N,N-diethylethylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (62 mg, yield 81%).

¹H-NMR (CDCl₃, 400 MHz): 0.96 (br, 6H), 2.52 (br, 4H), 2.67 (br, 2H), 3.68 (br, 2H), 4.07 (s, 6H), 7.26-7.54 (m, 7H), 7.83 (br, 1H), 8.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 456 (M⁺+1)

Example 517 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[2-(1-piperidinyl)ethyl]thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 2-(1-piperidinyl)ethylamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 14 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (35 mg, yield 45%).

¹H-NMR (CDCl₃, 400 MHz): 1.40-1.55 (m, 6H), 2.40-2.60 (m, 6H), 3.72 (m, 2H), 4.07 (s, 6H), 7.30-7.38 (m, 7H), 7.54 (s, 1H), 8.60 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 518 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[4-(1-benzylpiperidinyl)]thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 4-amino-1-benzylpiperidine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 14 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (40 mg, yield 44%).

¹H-NMR (CDCl₃, 400 MHz): 1.52 (m, 2H), 2.09 (m, 2H), 2.19 (m, 2H), 2.83 (m, 2H), 3.52 (s, 2H), 4.08 (s, 6H), 4.37 (m, 1H), 6.06 (d, J=7.8 Hz, 1H), 7.28-7.35 (m, 10H), 7.53 (s, 1H), 7.80 (br, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 530 (M⁺+1)

Example 519 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-acetamidomethyl)thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N-acetylethylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 14 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (13 mg, yield 17%).

¹H-NMR (CDCl₃, 400 MHz): 2.00 (s, 3H), 3.47 (m, 2H), 3.84 (m, 2H), 4.08 (s, 6H), 6.36 (br, 1H), 6.89 (br, 1H), 7.32-7.40 (m, 5H), 7.55 (s, 1H), 7.86 (br, 1H), 8.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 442 (M⁺+1)

Example 520 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(N-cyclohexylamino)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 7 hr. Next, cyclohexylhydrazine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 12 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (8 mg, yield 10%).

¹H-NMR (CDCl₃, 400 MHz): 1.20-2.27 (m, 16H), 3.83 (m, 1H), 4.06 (s, 6H), 5.51 (m, 1H), 6.34 (m, 1H), 7.00 (m, 1H), 7.18 (m, 1H), 7.36 (m, 1H), 7.43 (s, 1H), 7.61 (s, 1H), 8.46 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 521 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(1-piperidinyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 1-aminopiperidine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 14 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (20 mg, yield 27%).

¹H-NMR (CDCl₃, 400 MHz): 1.20-1.88 (m, 6H), 2.15 (s, 3H), 2.26 (s, 3H), 2.51 (m, 2H), 3.23 (m, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 6.33 (d, J=5.4 Hz, 1H), 6.93 (br, 1H), 7.03 (d, J=8.5 Hz, 1H), 7.47 (s, 1H), 7.57 (d, J=8.6 Hz, 1H), 7.62 (s, 1H), 8.46 (d, J=5.4 Hz, 1H), 9.00 (br, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 522 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-(1-piperidinyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 7 hr. Next, 1-aminopiperidine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 14 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (9 mg, yield 12%).

¹H-NMR (CDCl₃, 400 MHz): 1.20-1.90 (m, 6H), 2.18 (s, 3H), 2.27 (s, 3H), 2.50 (m, 2H), 3.21 (m, 2H), 4.07 (s, 6H), 6.38 (d, J=5.4 Hz, 1H), 6.86 (br, 1H), 6.98 (s, 1H), 7.49 (s, 1H), 7.59 (s, 1H), 7.79 (s, 1H), 8.47 (d, J=5.4 Hz, 1H), 9.05 (br, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 523 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-(N-cyclohexylamino)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (52 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 1.5 hr. Next, cyclohexylhydrazine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 7 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (10 mg, yield 13%).

¹H-NMR (CDCl₃, 400 MHz): 1.12-1.95 (m, 10H), 2.16 (s, 3H), 2.25 (s, 3H), 3.69 (m, 1H), 4.06 (s, 6H), 5.52 (m, 1H), 6.40 (d, J=5.4 Hz, 1H), 6.97 (m, 1H), 7.46 (s, 1H), 7.52 (s, 1H), 7.59 (s, 1H), 8.47 (d, J=5.4 Hz, 1H), 9.41 (br, 1H)

Mass spectrometry value (ESI-MS, m/z): 436 (?)

Example 524 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(1-piperidinyl]thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. Next, 1-aminopiperidine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 13 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (49 mg, yield 66%).

¹H-NMR (CDCl₃, 400 MHz): 1.18-1.83 (m, 6H), 2.48 (m, 2H), 3.18 (m, 2H), 4.07 (s, 3H), 4.08 (s, 3H), 6.99 (s, 1H), 7.26 (d, J=8.1 Hz, 2H), 7.34 (s, 1H), 7.56 (s, 1H), 7.76 (d, J=8.5 Hz, 2H), 7.53 (s, 1H), 8.61 (s, 1H), 9.27 (br, 1H)

Mass spectrometry value (ESI-MS, m/z): 440 (M⁺+1)

Example 525 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[3-(2-oxotetrahydro-1H-1-pyrrolyl)-propyl]thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (56 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 7 hr. Next, 1-(3-aminopropyl)pyrrolidone (50 mg) was added thereto, and the mixture was further stirred at room temperature for 13 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (15 mg, yield 17%).

¹H-NMR (CDCl₃, 400 MHz): 1.87 (m, 2H), 2.04 (m, 2H), 2.37 (t, J=8.2 Hz, 2H), 3.30 (t, J=6.2 Hz, 2H), 3.41 (t, J=7.2 Hz, 2H), 3.64 (m, 2H), 4.07 (s, 6H), 7.31-7.42 (m, 6H), 7.55 (s, 1H), 7.79 (br, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 482 (M⁺+1)

Example 526 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[3-(1-imidazoyl)propyl]thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (56 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 7 hr. Next, 3-(1-imidazoyl)propylamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 13 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (16 mg, yield 18%).

¹H-NMR (CDCl₃, 400 MHz): 2.29 (m, 2H), 3.69 (m, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 4.38 (m, 2H), 7.20-7.57 (m, 11H), 8.58 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 465 (M⁺+1)

Example 527 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[2-(1-morpholinyl)ethyl]thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (56 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 7 hr. Next, 2-(1-morpholinyl)ethylamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 13 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (9 mg, yield 10%).

¹H-NMR (CDCl₃, 400 MHz): 2.50 (m, 4H), 2.64 (m, 2H), 3.65 (m, 4H), 3.75 (m, 2H), 4.08 (s, 3H), 4.08 (s, 3H), 7.14 (br, 1H), 7.34 (m, 4H), 7.35 (s, 1H), 7.54 (s, 1H), 7.73 (br, 1H), 8.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 470 (M⁺+1)

Example 528 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-N′-{2-[N-ethyl-N-(o-tolyl)aminoethyl]thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (56 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 7 hr. Next, N-ethyl-N-(o-tolyl)ethylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 13 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (22 mg, yield 22%).

¹H-NMR (CDCl₃, 400 MHz): 1.11 (t, J=7.1 Hz, 3H), 2.29 (s, 2H), 3.34 (q, J=7.1H, 2H), 3.55 (t, J=6.3 Hz, 2H), 3.84 (m, 2H), 4.08 (s, 6H), 6.43 (br, 1H), 6.54-6.61 (m, 3H), 7.10 (m, 1H), 7.19 (d, J=8.8 Hz, 2H), 7.24 (d, J=8.8 Hz, 2H), 7.35 (s, 1H), 7.53 (s, 1H), 7.77 (br, 1H), 8.60 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 518 (M⁺+1)

Example 529 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-dimethylaminoethyl)thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 5 hr. Next, N,N-dimethylethylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (18 mg, yield 24%).

¹H-NMR (CDCl₃, 400 MHz): 1.83 (br, 2H), 2.26 (br, 6H), 2.55 (br, 2H), 4.07 (s, 6H), 7.29-7.30 (m, 5H), 7.34 (s, 1H), 7.54 (s, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 428 (M⁺+1)

Example 530 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[2-(1-pyrrolidyl)ethyl]thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 5 hr. Next, 2-(1-pyrrolidyl)ethylamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (16 mg, yield 21%).

¹H-NMR (CDCl₃, 400 MHz): 1.77 (br, 4H), 1.86 (br, 2H), 2.58 (br, 2H), 2.75 (br, 2H), 4.07 (s, 6H), 7.29-7.30 (m, 5H), 7.34 (s, 1H), 7.54 (s, 1H), 8.60 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 454 (M⁺+1)

Example 531 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(3-diethylaminopropyl)thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diethylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (10 mg, yield 12%).

¹H-NMR (CDCl₃, 400 MHz): 0.86 (br, 6H), 1.74 (br, 2H), 2.42 (br, 4H), 2.55 (br, 2H), 3.81 (br, 2H), 4.07 (s, 3H), 4.08 (s, 3H), 7.29 (s, 1H), 7.34 (m, 4H), 7.53 (s, 1H), 7.57 (br, 1H), 8.56 (s, 1H), 8.69 (br, 1H)

Mass spectrometry value (ESI-MS, m/z): 470 (M⁺+1)

Example 532 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-dibutylaminopropyl)thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diethylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (41 mg, yield 46%).

¹H-NMR (CDCl₃, 400 MHz): 0.87 (t, J=7.1 Hz, 6H), 1.19 (m, 8H), 1.71 (m, 2H), 2.28 (m, 4H), 2.52 (m, 2H), 3.79 (m, 2H), 4.07 (s, 3H), 4.08 (s, 3H), 7.27-7.32 (m, 4H), 7.34 (s, 1H), 7.52 (s, 1H), 7.75 (br, 1H), 8.44 (br, 1H), 8.57 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 526 (M⁺+1)

Example 533 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[3-(1-morpholino)propyl]thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 3-(1-morpholino)propylamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (16 mg, yield 20%).

¹H-NMR (CDCl₃, 400 MHz): 1.81 (m, 2H), 2.39 (m, 4H), 2.46 (m, 2H), 3.50 (m, 4H), 3.79 (m, 2H), 4.07 (s, 6H), 7.31-7.37 (m, 5H), 7.53 (s, 1H), 7.69 (br, 1H), 8.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 484 (M⁺+1)

Example 534 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-{3-[1-(2-methylpiperidinyl)]propyl}thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 3-[1-(2-methylpiperidinyl)]propylamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (30 mg, yield 36%).

¹H-NMR (CDCl₃, 400 MHz): 0.99 (d, J=6.4 Hz, 3H), 1.24-2.53 (m, 11H), 2.81 (m, 2H), 3.71 (m, 1H), 3.81 (m, 1H), 4.07 (s, 3H), 4.07 (s, 3H), 7.29-7.37 (m, 5H), 7.52 (s, 1H), 7.74 (br, 1H), 7.83 (br, 1H), 8.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 535 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-diisopropylaminoethyl)thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diisopropylethylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (47 mg, yield 58%). ¹H-NMR (CDCl₃, 400 MHz): 0.91 (br, 12H), 2.67 (br, 2H), 2.96 (br, 2H), 3.64 (br, 2H), 4.07 (s, 3H), 4.08 (s, 3H), 7.17 (br, 1H), 7.28-7.34 (m, 4H), 7.34 (s, 1H), 7.54 (s, 1H), 7.85 (br, 1H), 8.58 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 484 (M⁺+1)

Example 536 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-{3-[1-(4-methylpiperazinyl)]propylthiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 1 hr. Next, 1-(3-aminopropyl)-4-methylpiperazine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 6 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (6 mg, yield 7%).

¹H-NMR (CDCl₃, 400 MHz): 1.75-1.83 (m, 6H), 2.23 (s, 3H), 2.23 (m, 2H), 2.44 (m, 4H), 3.78 (br, 2H), 4.06 (s, 3H), 4.08 (s, 3H), 7.31-7.34 (m, 5H), 7.51 (s, 1H), 7.59 (br, 1H), 8.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 537 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[3-(1-pyrrolidinyl)propyl]thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 1 hr. Next, N,N-diethylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 6 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (19 mg, yield 24%).

¹H-NMR (CDCl₃, 400 MHz): 1.55 (br, 2H), 1.79 (m, 2H), 2.42 (br, 4H), 2.58 (br, 2H), 3.81 (br, 2H), 4.07 (s, 3H), 4.07 (s, 3H), 7.27-7.34 (m, 4H), 7.34 (s, 1H), 7.52 (s, 1H), 7.73 (br, 1H), 8.19 (br, 1H), 8.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 538 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-(2-dimethylaminoethyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-dimethylethylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (24 mg, yield 34%).

¹H-NMR (CDCl₃, 400 MHz): 2.16 (s, 3H), 2.22 (br, 6H), 2.28 (s, 3H), 2.51 (br, 2H), 3.68 (br, 2H), 4.06 (s, 3H), 4.06 (s, 3H), 6.27 (m, 1H), 6.68 (br, 1H), 7.05 (s, 1H), 7.21 (s, 1H), 7.44 (s, 1H), 7.49 (br, 1H), 7.57 (s, 1H), 8.46 (d, J=5.2 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 455 (M⁺+1)

Example 539 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-[3-(1-imidazoyl)propyl]thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 1-(3-aminopropyl)imidazole (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (20 mg, yield 25%).

¹H-NMR (CDCl₃, 400 MHz): 2.00 (m, 2H), 2.15 (m, 2H), 2.18 (s, 3H), 2.25 (s, 3H), 3.67 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 5.98 (br, 1H), 6.33 (d, J=5.4 Hz, 1H), 6.93 (s, 1H), 7.04 (s, 1H), 7.05 (s, 1H), 7.17 (s, 1H), 7.43 (s, 1H), 7.50 (br, 1H), 7.54 (s, 1H), 7.74 (s, 1H), 8.47 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 540 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-{2-[N-ethyl-N-(o-tolyl)amino]-ethyl}thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-dimethylethylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (28 mg, yield 32%).

¹H-NMR (CDCl₃, 400 MHz): 1.07 (t, J=7.1 Hz, 3H), 2.07 (s, 3H), 2.22 (s, 3H), 2.29 (s, 3H), 3.30 (q, J=7.1 Hz, 2H), 3.51 (t, J=6.0 Hz, 2H), 3.84 (m, 2H), 4.06 (s, 3H), 4.06 (s, 3H), 6.06 (br, 1H), 6.22 (d, J=5.4 Hz, 1H), 6.53-6.68 (m, 3H), 6.99 (s, 1H), 7.02 (s, 1H), 7.09 (m, 1H), 7.45 (s, 1H), 7.52 (br, 1H), 7.54 (s, 1H), 8.43 (d, J=5.2 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 545 (M⁺+1)

Example 541 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-[2-(1-pyrrolidinyl)ethyl]thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 1-(2-aminoethyl)pyrrolidine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (8 mg, yield 10%).

¹H-NMR (CDCl₃, 400 MHz): 1.72 (br, 4H), 2.16 (s, 3H), 2.27 (s, 3H), 2.54 (br, 4H), 2.73 (br, 2H), 3.72 (br, 2H), 4.06 (s, 6H), 6.28 (m, 1H), 6.77 (br, 1H), 7.04 (s, 1H), 7.19 (s, 1H), 7.43 (s, 1H), 7.56 (s, 1H), 8.46 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 542 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(2-dimethylaminoethyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 7 hr. Next, N,N-dimethylethylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 13 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (12 mg, yield 17%).

¹H-NMR (CDCl₃, 400 MHz): 2.16 (s, 3H), 2.19 (br, 6H), 2.28 (s, 3H), 2.48 (br, 2H), 3.66 (br, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 6.22 (m, 1H), 6.56 (br, 1H), 7.04 (d, J=8.3 Hz, 1H), 7.19 (d, J=8.5 Hz, 1H), 7.44 (s, 1H), 7.60 (s, 1H), 8.45 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 455 (M⁺+1)

Example 543 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-[3-(1-imidazoyl)propyl]thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 7 hr. Next, 1-(3-aminopropyl)imidazole (50 mg) was added thereto, and the mixture was further stirred at room temperature for 13 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (13 mg, yield 17%).

¹H-NMR (CDCl₃, 400 MHz): 2.14 (m, 2H), 2.18 (s, 3H), 2.26 (s, 3H), 3.66 (m, 2H), 4.04 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 5.79 (br, 1H), 6.30 (d, J=5.4 Hz, 1H), 6.92 (s, 1H), 7.04 (s, 1H), 7.05 (d, J=8.6 Hz, 1H), 7.14 (d, J=8.6 Hz, 1H), 7.44 (s, 1H), 7.51 (br, 1H), 7.56 (s, 1H), 7.62 (s, 1H), 8.47 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 544 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-{2-[N-ethyl-N-(o-tolyl amino]-ethyl}thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 7 hr. Next, N,N-dimethylethylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 13 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (4 mg, yield 4%).

¹H-NMR (CDCl₃, 400 MHz): 1.06 (t, J=7.1 Hz, 3H), 2.10 (s, 3H), 2.21 (s, 3H), 2.28 (s, 3H), 3.28 (q, J=7.1 Hz, 2H), 3.49 (t, J=6.1 Hz, 2H), 3.83 (m, 2H), 4.07 (s, 6H), 5.94 (br, 1H), 6.18 (d, J=5.1 Hz, 1H), 6.49-7.10 (m, 6H), 7.46 (s, 1H), 7.50 (br, 1H), 7.57 (s, 1H), 8.42 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 545 (M⁺+1)

Example 545 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-[2-(1-morpholino)ethyl]thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 1-(2-aminoethyl)morpholine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (23 mg, yield 29%).

¹H-NMR (CDCl₃, 400 MHz): 2.19 (s, 3H), 2.28 (s, 3H), 2.43 (br, 4H), 2.58 (m, 2H), 3.56 (m, 4H), 3.71 (m, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 6.30 (d, J=5.1 Hz, 1H), 6.60 (br, 1H), 7.07 (s, 1H), 7.21 (s, 1H), 7.45 (s, 1H), 7.46 (br, 1H), 7.56 (s, 1H), 8.48 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 546 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(3-diethylaminopropyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diethylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (36 mg, yield 45%).

¹H-NMR (CDCl₃, 400 MHz): 0.83 (t, J=7.1 Hz, 6H), 1.70 (m, 2H), 2.16 (s, 3H), 2.29 (s, 3H), 2.32 (m, 4H), 2.49 (m, 2H), 3.78 (m, 2H), 4.06 (s, 3H), 4.06 (s, 3H), 6.30 (d, J=5.4 Hz, 1H), 7.00 (d, J=8.5 Hz, 1H), 7.19 (d, J=8.5 Hz, 1H), 7.44 (s, 1H), 7.56 (br, 1H), 7.57 (s, 1H), 7.80 (br, 1H), 8.46 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 547 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(3-dibutylaminopropyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-dibutylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (33 mg, yield 37%).

¹H-NMR (CDCl₃, 400 MHz): 0.89 (t, J=6.8 Hz, 6H), 1.19 (m, 8H), 1.69 (m, 2H), 2.15 (s, 3H), 2.20 (m, 4H), 2.29 (s, 3H), 2.49 (m, 2H), 3.78 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 6.30 (d, J=5.1 Hz, 1H), 7.01 (d, J=8.6 Hz, 1H), 7.19 (d, J=8.5 Hz, 1H), 7.44 (s, 1H), 7.48 (br, 1H), 7.56 (s, 1H), 7.79 (br, 1H), 8.46 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 552 (M⁺+1)

Example 548 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-[3-(1-morpholino)propyl]thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 1-(3-aminopropyl)morpholine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (16 mg, yield 19%).

¹H-NMR (CDCl₃, 400 MHz): 1.78 (m, 4H), 2.19 (s, 3H), 2.29 (s, 3H), 2.36 (m, 4H), 3.45 (m, 4H), 3.78 (m, 2H), 4.06 (s, 3H), 4.06 (s, 3H), 6.33 (d, J=5.1 Hz, 1H), 6.70 (br, 1H), 7.03 (d, J=8.6 Hz, 1H), 7.19 (d, J=8.5 Hz, 1H), 7.44 (s, 1H), 7.56 (s, 1H), 8.48 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 511 (M⁺+1)

Example 549 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-[3-(2-methylpiperidinyl)propyl]-thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 1-(3-aminopropyl)-2-methylpiperidine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (39 mg, yield 47%).

¹H-NMR (CDCl₃, 400 MHz): 0.94-2.20 (m, 14H), 2.17 (s, 3H), 2.29 (s, 3H), 2.76 (m, 2H), 3.68 (m, 1H), 3.85 (m, 1H), 4.05 (s, 3H), 4.06 (s, 3H), 6.34 (d, J=5.1 Hz, 1H), 7.02 (d, J=8.6 Hz, 1H), 7.20 (d, J=8.3 Hz, 1H), 7.44 (s, 1H), 7.50 (br, 1H), 7.55 (s, 1H), 8.48 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺)

Example 550 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(2-diisopropylaminoethyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diisopropylethylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (52 mg, yield 64%).

¹H-NMR (CDCl₃, 400 MHz): 0.84 (br, 12H), 2.13 (s, 3H), 2.27 (s, 3H), 2.62 (m, 2H), 2.89 (m, 2H), 3.61 (m, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 6.24 (m, 1H), 7.02 (d, J=8.5 Hz, 1H), 7.18 (d, J=8.3 Hz, 1H), 7.44 (s, 1H), 7.52 (br, 1H), 7.58 (s, 1H), 8.44 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 511 (M⁺+1)

Example 551 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-(3-diethylaminopropyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diethylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (38 mg, yield 49%).

¹H-NMR (CDCl₃, 400 MHz): 0.86 (t, J=7.2 Hz, 6H), 1.72 (m, 2H), 2.16 (s, 3H), 2.27 (s, 3H), 2.34 (m, 4H), 2.51 (m, 2H), 3.79 (m, 2H), 4.06 (s, 6H), 6.34 (d, J=5.1 Hz, 1H), 7.01 (s, 1H), 7.21 (s, 1H), 7.38 (br, 1H), 7.44 (s, 1H), 7.54 (s, 1H), 7.93 (br, 1H), 8.48 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 552 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-(3-dibutylaminopropyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-dibutylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (34 mg, yield 40%).

¹H-NMR (CDCl₃, 400 MHz): 0.90 (t, J=7.0 Hz, 6H), 1.20 (m, 8H), 1.70 (m, 2H), 2.16 (s, 3H), 2.23 (m, 4H), 2.27 (s, 3H), 2.51 (m, 2H), 3.79 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 6.34 (d, J=5.2 Hz, 1H), 7.02 (s, 1H), 7.20 (s, 1H), 7.30 (br, 1H), 7.44 (s, 1H), 7.54 (s, 1H), 7.88 (br, 1H), 8.48 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 553 (M⁺+1)

Example 553 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-[3-(1-morpholino)propyl]thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 1-(3-aminopropyl)morpholine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (18 mg, yield 23%).

¹H-NMR (CDCl₃, 400 MHz): 1.78 (m, 4H), 2.19 (s, 3H), 2.27 (s, 3H), 2.36 (m, 4H), 3.45 (m, 4H), 3.79 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 6.37 (d, J=5.4 Hz, 1H), 6.83 (br, 1H), 7.03 (s, 1H), 7.22 (s, 1H), 7.44 (s, 1H), 7.54 (s, 1H), 8.50 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 511 (M⁺+1)

Example 554 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-[3-(2-methylpiperidinyl)propyl]-thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 1-(3-aminopropyl)-2-methylpiperidine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (46 mg, yield 56%).

¹H-NMR (CDCl₃, 400 MHz): 0.90-2.20 (m, 14H), 2.17 (s, 3H), 2.27 (s, 3H), 2.79 (m, 2H), 3.68 (m, 1H), 3.88 (m, 1H), 4.04 (s, 3H), 4.06 (s, 3H), 6.39 (d, J=5.2 Hz, 1H), 7.02 (s, 1H), 7.22 (s, 1H), 7.38 (br, 1H), 7.44 (s, 1H), 7.53 (s, 1H), 8.49 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺)

Example 555 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-(2-diisopropylaminoethyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diisopropylethylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (13 mg, yield 17%).

¹H-NMR (CDCl₃, 400 MHz): 0.86 (br, 12H), 2.14 (s, 3H), 2.26 (s, 3H), 2.62 (m, 2H), 2.91 (m, 2H), 3.61 (m, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 6.27 (m, 1H), 6.68 (br, 1H), 7.03 (s, 1H), 7.19 (s, 1H), 7.36 (br, 1H), 7.44 (s, 1H), 7.56 (s, 1H), 8.46 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 511 (M⁺+1)

Example 556 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-[3-(4-methylpiperazinyl)propyl]-thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 1-(3-aminopropyl)-4-methylpiperazine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (20 mg, yield 24%).

¹H-NMR (CDCl₃, 400 MHz): 1.76 (m, 6H), 2.17 (s, 3H), 2.26 (m, 2H), 2.28 (s, 3H), 2.41 (m, 4H), 3.77 (m, 2H), 4.03 (s, 3H), 4.06 (s, 3H), 6.34 (d, J=5.1 Hz, 1H), 6.83 (br, 1H), 7.05 (s, 1H), 7.22 (s, 1H), 7.37 (br, 1H), 7.44 (s, 1H), 7.52 (s, 1H), 8.48 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 524 (M⁺+1)

Example 557 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-[3-(4-methylpiperazinyl)propyl]-thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 1-(3-aminopropyl)-4-methylpiperazine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (10 mg, yield 11%).

¹H-NMR (CDCl₃, 400 MHz): 1.73 (m, 6H), 2.17 (s, 3H), 2.25 (m, 2H), 2.29 (s, 3H), 2.39 (m, 4H), 3.77 (m, 2H), 4.04 (s, 3H), 4.06 (s, 3H), 6.30 (d, J=5.1 Hz, 1H), 6.76 (br, 1H), 7.05 (d, J=8.6 Hz, 1H), 7.20 (d, J=8.6 Hz, 1H), 7.38 (br, 1H), 7.44 (s, 1H), 7.55 (s, 1H), 8.47 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 524 (M⁺+1)

Example 558 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-[3-(1-piperidinyl)propyl]thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, 1-(3-aminopropyl)pyrrolidine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (18 mg, yield 22%).

¹H-NMR (CDCl₃, 400 MHz): 1.55 (br, 4H), 1.77 (br, 2H), 2.17 (s, 3H), 2.28 (s, 3H), 2.39 (br, 4H), 2.55 (br, 2H), 3.78 (br, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 6.32 (d, J=5.4 Hz, 1H), 7.00 (d, J=8.6 Hz, 1H), 7.18 (m, 1H), 7.44 (s, 1H), 7.46 (br, 1H), 7.56 (s, 1H), 8.47 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 475

Example 559 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-dimethylaminoethyl)thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 5 hr. Next, N,N-dimethylethylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (62 mg, yield 83%).

¹H-NMR (CDCl₃, 400 MHz): 2.52 (s, 6H), 2.67 (br, 2H), 3.68 (br, 2H), 4.07 (s, 6H), 7.26-7.54 (m, 7H), 7.83 (br, 1H), 8.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 428 (M⁺+1)

Example 560 N-(1-Benzyltetrahydro-1H-3-pyrrolyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}urea

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. 1-Benzyl-3-aminopyrrolidine (89 mg) was then added thereto, and the mixture was stirred at room temperature for 3 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (76 mg, yield 45%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.97-2.08 (m, 1H), 2.38-2.49 (m, 1H), 2.55-2.64 (m, 1H), 2.78-2.85 (m, 1H), 3.13-3.19 (m, 1H), 3.34-3.41 (m, 1H), 3.91 (s, 1H), 3.92 (s, 1H), 4.04 (s, 6H), 4.45-4.53 (m, 1H), 6.23 (br, 1H), 6.44 (d, J=5.4 Hz, 1H), 7.07-7.11 (m, 2H), 7.35-7.47 (m, 8H), 7.56 (s, 1H), 8.46 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 499 (M⁺+1)

Example 561 Ethyl 4-[({4-[(6,7-dimethoxy-4-quinolyl)oxy]anilino}carbonyl)amino]-1-piperidinecarboxylate

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. Ethyl 4-amino-1-piperidine (87 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (108 mg, yield 65%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.25 (t, J=7.1 Hz, 3H), 1.32-1.45 (m, 2H), 1.93-2.02 (m, 2H), 2.92-3.05 (m, 2H), 3.83-3.94 (m, 1H), 3.98-4.06 (m, 2H), 4.07 (s, 3H), 4.08 (s, 3H), 4.09-4.16 (m, 2H), 5.57 (d, J=7.8 Hz, 1H), 6.48 (d, J=5.9 Hz, 1H), 7.05-7.10 (m, 2H), 7.50-7.55 (m, 2H), 7.58 (s, 1H), 7.59 (s, 1H), 7.74 (s, 1H), 8.36 (d, J=5.9 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 495 (M⁺+1)

Example 562 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2,2,6,6-tetramethyl-4-piperidyl)urea

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. 4-Amino-2,2,6,6-tetramethylpiperidine (79 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (27 mg, yield 17%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.53-2.09 (m, 16H), 4.02 (s, 3H), 4.06 (s, 3H), 4.22-4.37 (m, 1H), 6.51 (d, J=5.6 Hz, 1H), 7.05 (d, J=8.8 Hz, 2H), 7.42 (s, 1H), 7.54-7.64 (m, 3H), 8.42 (d, J=5.9 Hz, 1H), 8.65 (br, 1H)

Mass spectrometry value (ESI-MS, m/z): 479 (M⁺+1)

Example 563 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2,2,6,6-tetramethyl-4-piperidyl)urea

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. 4-Amino-2,2,6,6-tetramethylpiperidine (79 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (66 mg, yield 41%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.28-2.09 (m, 16H), 4.05 (s, 3H), 4.06 (s, 3H), 4.11-4.28 (m, 1H), 7.13 (d, J=8.8 Hz, 2H), 7.29 (s, 1H), 7.46-7.55 (m, 3H), 8.57 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 564 N-[(3R)-1-Benzyltetrahydro-1H-3-pyrrolyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-urea

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. (3R)-(−)-1-Benzyl-3-aminopyrrolidine (89 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (54 mg, yield 32%).

¹H-NMR (chloroform-d, 400 MHz): δ 2.00-2.16 (m, 2H), 2.41-2.52 (m, 1H), 2.63-2.72 (m, 1H), 2.84-2.92 (m, 1H), 3.21-3.29 (m, 1H), 3.99 (s, 1H), 4.01 (s, 1H), 4.04 (s, 3H), 4.05 (s, 3H), 4.50-4.61 (m, 1H), 6.44 (d, J=5.1 Hz, 1H), 7.06-7.12 (m, 2H), 7.37-7.48 (m, 8H), 7.56 (s, 1H), 8.46 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 499 (M⁺+1)

Example 565 N-[(3S)-1-Benzyltetrahydro-1H-3-pyrrolyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-urea

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. (3S)-(+)-1-Benzyl-3-aminopyrrolidine (89 mg) was then added thereto, and the mixture was stirred at room temperature for 5 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (48 mg, yield 29%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.92-2.17 (m, 2H), 2.40-2.51 (m, 1H), 2.60-2.71 (m, 1H), 2.81-2.90 (m, 1H), 3.18-3.25 (m, 1H), 3.96 (s, 1H), 3.98 (s, 1H), 4.05 (s, 6H), 4.49-4.58 (m, 1H), 6.44 (d, J=5.1 Hz, 1H), 7.06-7.12 (m, 2H), 7.37-7.49 (m, 7H), 7.56 (s, 1H), 7.61 (s, 1H), 8.46 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 499 (M⁺+1)

Example 566 N-[(3R)-1-Benzyltetrahydro-1H-3-pyrrolyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-phenyl}urea

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. (3R)-(−)-1-Benzyl-3-aminopyrrolidine (89 mg) was then added thereto, and the mixture was stirred at room temperature for 5 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (114 mg, yield 68%).

¹H-NMR (chloroform-d, 400 MHz): δ 2.07-2.20 (m, 1H), 2.40-2.52 (m, 1H), 2.76-2.87 (m, 1H), 2.99-3.07 (m, 1H), 3.29-3.38 (m, 1H), 3.51-3.60 (m, 1H), 4.06 (s, 6H), 4.08 (s, 1H), 4.10 (s, 1H), 4.57-4.66 (m, 1H), 6.75-6.85 (m, 1H), 7.11-7.17 (m, 2H), 7.29-7.57 (m, 9H), 8.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 500 (M⁺+1)

Example 567 N-[(3S)-1-Benzyltetrahydro-1H-3-pyrrolyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-phenyl}urea

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. (3S)-(+)-1-Benzyl-3-aminopyrrolidine (89 mg) was then added thereto, and the mixture was stirred at room temperature for 5 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (100 mg, yield 60%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.97-2.08 (m, 1H), 2.33-2.48 (m, 1H), 2.60-2.69 (m, 1H), 2.82-2.91 (m, 1H), 3.11-3.20 (m, 1H), 3.32-3.42 (m, 1H), 3.94 (s, 1H), 3.96 (s, 1H), 4.06 (s, 6H), 4.46-4.57 (m, 1H), 6.37 (br, 1H), 7.12-7.18 (m, 2H), 7.29-7.50 (m, 8H), 7.54 (s, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 500 (M⁺+1)

Example 568 N-{4-[(6,7-Dimethoxy-4-quinolyl)-oxy]phenyl}-N′-[1-(2-methylbenzyl)-4-piperidyl]urea

N-(1-Benzyl-4-piperidyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}urea (100 mg) was dissolved in 1,2-dichloroethane (25 ml) to prepare a solution. 1-Chloroethyl chloroformate (0.10 ml) was then added to the solution, and the mixture was heated under reflux overnight. The solvent was removed by distillation under the reduced pressure. Methanol (20 ml) was added to the residue, followed by heating under reflux for 2 hr. The solvent was removed by distillation under the reduced pressure to give 139 mg of N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(4-piperidyl)urea (1).

Acetonitrile (10 ml) was added to the compound (1) (139 mg), 2-methylbenzyl bromide (0.03 ml), and potassium carbonate (81 mg), and the mixture was stirred at room temperature overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (46 mg, yield 45%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.88-2.01 (m, 2H), 2.09-2.19 (m, 2H), 2.42 (s, 3H), 2.53-2.67 (m, 2H), 3.19-3.29 (m, 2H), 3.30-3.39 (m, 1H), 3.90 (s, 2H), 4.04 (s, 3H), 4.04 (s, 3H), 6.42 (d, J=5.4 Hz, 1H), 7.05-7.12 (m, 2H), 7.17-7.27 (m, 4H), 7.42 (s, 1H), 7.47-7.53 (m, 2H), 7.55 (s, 1H), 7.56 (s, 1H), 8.45 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 527 (M⁺+1)

Example 569 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[1-(2-methylbenzyl)tetrahydro-1H-3-pyrrolyl]urea

3-Aminopyrrolidine (500 mg) was dissolved in acetonitrile (10 ml) to prepare a solution. 2-Methylbenzyl bromide (0.78 ml) and potassium carbonate (2.40 g) were added to the solution, and the mixture was stirred at room temperature for 3 hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform/methanol for development to give 1-(2-methylbenzyl)-3-pyrrolidinamine (1) (604 mg, yield 55%).

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. The compund (1) (96 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (64 mg, yield 37%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.95-2.05 (m, 1H), 2.41 (s, 3H), 2.40-2.48 (m, 1H), 2.55-2.63 (m, 1H), 2.79-2.87 (m, 1H), 3.08-3.14 (m, 1H), 3.30-3.38 (m, 1H), 3.90 (s, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 4.44-4.55 (m, 1H), 7.13-7.18 (m, 2H), 7.18-7.40 (m, 5H), 7.40-7.47 (m, 2H), 7.55 (s, 1H), 8.60 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 514 (M⁺+1)

Example 570 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-nitrophenyl}-N′-[1-(2-methylbenzyl)tetrahydro-1H-3-pyrrolyl]urea

Chloroform (13 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) to prepare a solution. Triphosgene (96 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. 1-(2-Methylbenzyl)-3-pyrrolidinamine (83 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (38 mg, yield 23%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.94-2.04 (m, 1H), 2.44 (s, 3H), 2.42-2.50 (m, 1H), 2.55-2.65 (m, 1H), 2.81-2.90 (m, 1H), 3.02-3.10 (m, 1H), 3.27-3.34 (m, 1H), 3.88-3.92 (m, 2H), 4.07 (s, 3H), 4.09 (s, 3H), 4.50-4.59 (m, 1H), 7.18-7.26 (m, 2H), 7.32-7.43 (m, 2H), 7.49-7.55 (m, 2H), 8.12 (d, J=2.7 Hz, 1H), 8.60 (s, 1H), 8.71-8.77 (m, 1H), 9.78 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 559 (M⁺+1)

Example 571 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-methoxyphenyl}-N′-[1-(2-methylbenzyl)tetrahydro-1H-3-pyrrolyl]urea

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) to prepare a solution. Triphosgene (99 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. 1-(2-Methylbenzyl)-3-pyrrolidinamine (87 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (58 mg, yield 35%).

¹H-NMR (chloroform-d, 400 MHz): δ 2.01-2.11 (m, 1H), 2.21-2.33 (m, 1H), 2.50 (s, 3H), 2.48-2.58 (m, 1H), 2.86-2.98 (m, 1H), 3.43-3.52 (m, 1H), 3.68-3.78 (m, 1H), 3.84 (s, 3H), 4.07 (s, 6H), 4.21 (s, 1H), 4.23 (s, 1H), 4.71-4.82 (m, 1H), 6.75 (d, J=2.4 Hz, 1H), 6.79 (dd, J=2.4 Hz, 8.8 Hz, 1H), 7.17-7.22 (m, 1H), 7.27-7.36 (m, 3H), 7.54 (s, 1H), 7.54-7.59 (m, 1H), 8.13 (d, J=8.8 Hz, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 544 (M⁺+1)

Example 572 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-[1-(2-methylbenzyl)tetrahydro-1H-3-pyrrolyl]urea

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) to prepare a solution. Triphosgene (101 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. 1-(2-Methylbenzyl)-3-pyrrolidinamine (88 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (68 mg, yield 41%).

¹H-NMR (chloroform-d, 400 MHz): δ 2.01-2.10 (m, 1H), 2.11 (s, 3H), 2.22 (s, 3H), 2.36 (s, 3H), 2.38-2.47 (m, 1H), 2.50-2.59 (m, 1H), 2.73-2.81 (m, 1H), 3.01-3.09 (m, 1H), 3.23-3.33 (m, 1H), 3.86 (s, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 4.48-4.58 (m, 1H), 6.30 (d, J=5.4 Hz, 1H), 6.97 (d, J=8.8 Hz, 1H), 7.14-7.36 (m, 4H), 7.44 (s, 1H), 7.62 (s, 1H), 8.44 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 541 (M⁺+1)

Example 573 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-[1-(2-methylbenzyl)tetrahydro-1H-3-pyrrolyl]urea

Chloroform (10 ml) and triethylamine (2 ml) were added to 2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (100 mg) to prepare a solution. Triphosgene (99 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. 1-(2-Methylbenzyl)-3-pyrrolidinamine (86 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (82 mg, yield 50%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.92-2.01 (m, 1H), 2.39-2.47 (m, 1H), 2.41 (s, 3H), 2.51-2.60 (m, 1H), 2.77-2.84 (m, 1H), 3.01-3.08 (m, 1H), 3.23-3.33 (m, 1H), 3.86 (s, 1H), 3.87 (s, 1H), 4.07 (s, 6H), 4.27-4.38 (m, 1H), 7.12-7.40 (m, 7H), 7.51 (s, 1H), 8.19 (d, J=9.0 Hz, 1H), 8.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 548 (M⁺+1)

Example 574 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[1-(2-methylbenzyl)tetrahydro-1H-3-pyrrolyl]-urea

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. 1-(2-Methylbenzyl)-3-pyrrolidinamine (96 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (101 mg, yield 59%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.98-2.10 (m, 1H), 2.38-2.50 (m, 1H), 2.41 (s, 3H), 2.58-2.68 (m, 1H), 2.83-2.93 (m, 1H), 3.15-3.22 (m, 1H), 3.37-3.44 (m, 1H), 3.95 (s, 2H), 4.04 (s, 6H), 4.46-4.58 (m, 1H), 6.43 (d, J=5.4 Hz, 1H), 7.05-7.12 (m, 2H), 7.18-7.47 (m, 7H), 7.56 (s, 1H), 8.46 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 513 (M⁺+1)

Example 575 N-[(3R)-1-Benzyltetrahydro-1H-3-pyrrolyl]-N′-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}urea

Chloroform (15 ml) and triethylamine (3 ml) were added to 2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (200 mg) to prepare a solution. Triphosgene (198 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. (3R)-(−)-1-Benzyl-3-aminopyrrolidine (80 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (189 mg, yield 59%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.90-2.02 (m, 1H), 2.37-2.47 (m, 1H), 2.48-2.58 (m, 1H), 2.72-2.80 (m, 1H), 2.98-3.06 (m, 1H), 3.21-3.29 (m, 1H), 3.83 (s, 1H), 3.85 (s, 1H), 4.07 (s, 6H), 4.45-4.56 (m, 1H), 7.14 (dd, J=2.7 Hz, 9.0 Hz, 1H), 7.28-7.43 (m, 7H), 7.51 (s, 1H), 8.20 (d, J=9.0 Hz, 1H), 8.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 576 N-[(3S)-1-Benzyltetrahydro-1H-3-pyrrolyl]-N′-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}urea

Chloroform (15 ml) and triethylamine (3 ml) were added to 2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (200 mg) to prepare a solution. Triphosgene (198 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. (3S)-(+)-1-Benzyl-3-aminopyrrolidine (80 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (204 mg, yield 63%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.90-2.00 (m, 1H), 2.35-2.48 (m, 1H), 2.50-2.58 (m, 1H), 2.73-2.80 (m, 1H), 2.98-3.05 (m, 1H), 3.20-3.29 (m, 1H), 3.83 (s, 1H), 3.85 (s, 1H), 4.07 (s, 6H), 4.45-4.54 (m, 1H), 7.15 (dd, J=2.7 Hz, 9.0 Hz, 1H), 7.28-7.43 (m, 7H), 7.51 (s, 1H), 8.20 (d, J=9.0 Hz, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 577 N-[(3R)-1-Benzyltetrahydro-1H-3-pyrrolyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}urea

Chloroform (27 ml) and triethylamine (4 ml) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (200 mg) to prepare a solution. Triphosgene (192 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. (3R)-(−)-1-Benzyl-3-aminopyrrolidine (77 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (184 mg, yield 58%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.96-2.05 (m, 1H), 2.39-2.49 (m, 1H), 2.56-2.66 (m, 1H), 2.81-2.89 (m, 1H), 3.04-3.12 (m, 1H), 3.26-3.36 (m, 1H), 3.91 (s, 2H), 4.07 (s, 6H), 4.50-4.59 (m, 1H), 7.30-7.55 (m, 7H), 8.12 (d, J=2.9 Hz, 1H), 8.60 (s, 1H), 8.73 (d, J=9.3 Hz, 1H), 9.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 545 (M⁺+1)

Example 578 N-[(3S)-1-Benzyltetrahydro-1H-3-pyrrolyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}urea

Chloroform (27 ml) and triethylamine (4 ml) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (200 mg) to prepare a solution. Triphosgene (192 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. (3S)-(+)-1-Benzyl-3-aminopyrrolidine (77 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (153 mg, yield 48%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.95-2.07 (m, 1H), 2.39-2.49 (m, 1H), 2.57-2.67 (m, 1H), 2.82-2.90 (m, 1H), 3.04-3.12 (m, 1H), 3.27-3.36 (m, 1H), 3.92 (s, 2H), 4.07 (s, 6H), 4.50-4.60 (m, 1H), 7.29-7.55 (m, 7H), 8.12 (d, J=2.9 Hz, 1H), 8.60 (s, 1H), 8.73 (d, J=9.5 Hz, 1H), 9.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 545 (M⁺+1)

Example 579 N-[1-(2-Chlorobenzyl)tetrahydro-1H-3-pyrrolyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-urea

3-Aminopyrrolidine (500 mg) was dissolved in acetonitrile (10 ml) to prepare a solution. 2-Chlorobenzyl bromide (0.75 ml), potassium carbonate (2.40 g) were added to the solution, and the mixture was stirred at room temperature for one hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform/methanol for development to give 1-(2-chlorobenzyl)-3-pyrrolidinamine (1) (453 mg, yield 37%).

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. The compound (1) (106 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (76 mg, yield 42%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.93-2.03 (m, 1H), 2.39-2.49 (m, 1H), 2.58-2.69 (m, 1H), 2.84-2.92 (m, 1H), 3.11-3.18 (m, 1H), 3.32-3.40 (m, 1H), 4.05 (s, 6H), 4.45-4.53 (m, 1H), 6.44 (d, J=5.4 Hz, 1H), 7.05-7.12 (m, 2H), 7.27-7.34 (m, 2H), 7.38-7.47 (m, 4H), 7.54-7.64 (m, 2H), 8.46 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 533 (M⁺+1)

Example 580 N-[1-(2-Chlorobenzyl)tetrahydro-1H-3-pyrrolyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-phenyl}urea

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. 1-(2-Chlorobenzyl)-3-pyrrolidinamine (106 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (109 mg, yield 61%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.86-1.97 (m, 1H), 2.34-2.47 (m, 1H), 2.51-2.61 (m, 1H), 2.78-2.85 (m, 1H), 3.00-3.07 (m, 1H), 3.21-3.29 (m, 1H), 3.98 (s, 2H), 4.07 (s, 6H), 4.40-4.50 (m, 1H), 5.80-5.90 (m, 1H), 7.13-7.18 (m, 2H), 7.25-7.46 (m, 6H), 7.53-7.57 (m, 2H), 8.60 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 581 N-[1-(2-Chlorobenzyl)tetrahydro-1H-3-pyrrolyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}urea

Chloroform (13 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) to prepare a solution. Triphosgene (96 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. 1-(2-Chlorobenzyl)-3-pyrrolidinamine (92 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (66 mg, yield 39%).

¹H-NMR (chloroform-d, 400 MHz): δ 2.05-2.16 (m, 1H), 2.40-2.50 (m, 1H), 2.60-2.69 (m, 1H), 2.87-2.93 (m, 1H), 3.03-3.10 (m, 1H), 3.25-3.33 (m, 1H), 4.04 (s, 2H), 4.07 (s, 6H), 4.51%-4.60 (m, 1H), 7.26-7.56 (m, 5H), 7.62-7.68 (m, 1H), 8.12 (d, J=2.7 Hz, 1H), 8.60 (s, 1H), 8.74 (d, J=9.3 Hz, 1H), 9.79 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 579 (M⁺+1)

Example 582 N-{1-[4-(Tert-butyl)benzyl]tetrahydro-1H-3-pyrrolyl}-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-phenyl}urea

3-Aminopyrrolidine (500 mg) was dissolved in acetonitrile (10 ml) to prepare a solution. 4-(Tert-butyl)benzyl bromide (1.07 ml) and potassium carbonate (2.40 g) were added to the solution, and the mixture was stirred at room temperature for one hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform/methanol for development to give 1-[4-(tert-butyl)benzyl]-3-pyrrolidinamine (1) (589 mg, yield 44%).

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. (1) (117 mg) was then added thereto, and the mixture was stirred at room temperature for 5 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (71 mg, yield 38%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.32 (s, 9H), 2.12-2.28 (m, 1H), 2.43-2.55 (m, 1H), 2.83-2.93 (m, 1H), 3.01-3.09 (m, 1H), 3.38-3.45 (m, 1H), 3.62-3.72 (m, 1H), 4.04 (s, 3H), 4.04 (s, 3H), 4.11 (s, 1H), 4.13 (s, 1H), 4.61-4.70 (m, 1H), 6.43 (d, J=5.4 Hz, 1H), 7.04-7.10 (m, 2H), 7.38-7.58 (m, 8H), 8.45 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 555 (M⁺+1)

Example 583 N-{1-[4-(Tert-butyl)benzyl]tetrahydro-1H-3-pyrrolyl}-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)-oxy]phenyl}urea

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. 1-[4-(Tert-butyl)benzyl]-3-pyrrolidinamine (117 mg) was then added thereto, and the mixture was stirred at room temperature for 5 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (76 mg, yield 41%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.31 (s, 9H), 2.07-2.12 (m, 1H), 2.37-2.48 (m, 1H), 2.57-2.66 (m, 1H), 2.78-2.88 (m, 1H), 3.11-3.19 (m, 1H), 3.32-3.42 (m, 1H), 3.89 (s, 1H), 3.91 (s, 1H), 4.06 (s, 6H), 4.44-4.55 (m, 1H), 7.12-7.17 (m, 2H), 7.28-7.57 (m, 8H)₁ 8.60 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 556 (M⁺+1)

Example 584 N-{1-[4-(Tert-butyl)benzyl]tetrahydro-1H-3-pyrrolyl}-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)-oxy]-2-nitrophenyl}urea

Chloroform (13 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) to prepare a solution. Triphosgene (96 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. 1-[4-(Tert-butyl)benzyl]-3-pyrrolidinamine (102 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (38 mg, yield 22%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.32 (s, 9H), 1.92-2.04 (m, 1H), 2.38-2.48 (m, 1H), 2.53-2.64 (m, 1H), 2.78-2.86 (m, 1H), 3.03-3.11 (m, 1H), 3.27-3.35 (m, 1H), 3.86 (s, 1H), 3.87 (s, 1H), 4.07 (s, 6H), 4.50-4.58 (m, 1H), 7.32-7.54 (m, 6H), 8.12 (d, J=2.9 Hz, 1H), 8.60 (s, 1H), 8.71-8.75 (m, 1H), 9.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 601 (M⁺+1)

Example 585 N-[1-(Cyclohexylmethyl)tetrahydro-1H-3-pyrrolyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-phenyl}urea

3-Aminopyrrolidine (500 mg) was dissolved in acetonitrile (10 ml) to prepare a solution. Cyclohexylmethyl bromide (0.81 ml), potassium carbonate (2.40 g), and tetra-n-butylammonium iodide (100 mg) were added to the solution, and the mixture was stirred at room temperature for 7 hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform/methanol for development to give 1-(cyclohexylmethyl)-3-pyrrolidinamine (1) (271 mg, yield 26%).

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. The compound (1) (74 mg) was then added thereto, and the mixture was stirred at room temperature for 3 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (85 mg, yield 50%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.00-1.32 (m, 6H), 1.64-1.85 (m, 4H), 1.91-2.03 (m, 2H), 2.27-2.38 (m, 1H), 2.48-2.60 (m, 1H), 2.88-2.98 (m, 2H), 3.65-3.73 (m, 1H), 4.04 (s, 6H), 4.05 (s, 2H), 4.68-4.78 (m, 1H), 6.44 (d, J=5.4 Hz, 1H), 7.06-7.11 (m, 2H), 7.42 (s, 1H), 7.47-7.55 (m, 2H), 7.56 (s, 1H), 8.46 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 505 (M⁺+1)

Example 586 N-[1-(cyclohexylmethyl)tetrahydro-1H-3-pyrrolyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-phenyl}urea

Chloroform (10 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) to prepare a solution. Triphosgene (110 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. 1-(Cyclohexylmethyl)-3-pyrrolidinamine (74 mg) was then added thereto, and the mixture was stirred at room temperature for 3 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (94 mg, yield 55%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.00-1.37 (m, 6H), 1.63-1.88 (m, 4H), 1.90-1.98 (m, 1H), 2.27-2.39 (m, 1H), 2.47-2.60 (m, 1H), 2.84-3.01 (m, 2H), 3.07-3.18 (m, 1H), 3.68-3.78 (m, 1H), 3.95-4.06 (m, 2H), 4.07 (s, 3H), 4.08 (s, 3H), 4.70-4.79 (m, 1H), 7.10-7.17 (m, 2H), 7.41 (s, 1H), 7.52 (s, 1H), 7.52-7.58 (m, 2H), 7.88 (s, 1H), 8.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 587 N-[1-(Cyclohexylmethyl)tetrahydro-1H-3-pyrrolyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}urea

Chloroform (13 ml) and triethylamine (2 ml) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) to prepare a solution. Triphosgene (96 mg) was added to the solution, and the mixture was stirred at room temperature for 30 min. 1-(Cyclohexylmethyl)-3-pyrrolidinamine (64 mg) was then added thereto, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (34 mg, yield 21%).

¹H-NMR (chloroform-d, 400 MHz): δ 0.94-1.34 (m, 6H), 1.61-1.81 (m, 4H), 1.87-1.99 (m, 2H), 2.06-2.20 (m, 1H), 2.40-2.52 (m, 1H), 2.61-2.73 (m, 2H), 2.83-2.93 (m, 1H), 3.28-3.40 (m, 1H), 3.52-3.63 (m, 1H), 4.07 (s, 6H), 4.57-4.68 (m, 1H), 7.33 (s, 1H), 7.51 (s, 2H), 8.12 (d, J=2.9 Hz, 1H), 8.60 (s, 1H), 8.72 (d, J=9.3 HZ, 1H), 9.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 551 (M⁺+1)

Example 588 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-diethylaminopropyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diethylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 14 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (25 mg, yield %).

¹H-NMR (CDCl₃, 400 MHz): 1.00-1.10 (m, 6H), 1.85-2.00 (m, 2H), 2.55-2.80 (m, 6H), 3.80-3.90 (m, 2H), 4.04 (s, 3H), 4.06 (s, 3H), 6.54 (d, J=5.4 Hz, 1H), 7.19 (d, J=6.8 Hz, 1H), 7.24-7.28 (m, 2H), 7.36-7.44 (m, 2H), 7.44 (s, 1H), 7.516 (s, 1H), 8.51 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 469 (M⁺+1)

Example 589 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-diethylaminoethyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diethylethylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 14 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (25 mg, yield 33%).

¹H-NMR (CDCl₃, 400 MHz): 0.90-1.10 (m, 6H), 2.45-2.75 (m, 2H), 3.60-3.75 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 6.49 (s, 1H), 7.20-7.38 (m, 4H), 7.43 (s, 1H), 7.53 (s, 1H), 8.50 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 455 (M⁺+1)

Example 590 N-{4-[(6,7-Dimethoxy-4-quinolyl)-oxy]phenyl}-N′-[4-(N-benzyl)piperidinyl]urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-amino-1-benzylpiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (27 mg, yield 32%).

¹H-NMR (CDCl₃, 400 MHz): 1.45-1.55 (m, 2H), 1.95-2.05 (m, 2H), 2.13-2.23 (m, 2H), 2.80-2.90 (m, 2H), 3.52 (s, 2H), 3.70-3.80 (m, 1H), 4.04 (s, 6H), 4.85-4.95 (m, 1H), 6.44 (d, J=5.4 Hz, 1H), 6.80-6.82 (m, 2H), 7.10-7.14 (m, 2H), 7.26-7.34 (m, 5H), 7.40-7.44 (m, 2H), 7.55 (s, 1H), 8.46 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 513 (M⁺+1)

Example 591 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[4-(N-benzyl)piperidinyl]urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-amino-1-benzylpiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (30 mg, yield 35%).

¹H-NMR (CDCl₃, 400 MHz): 1.45-1.60 (m, 2H), 1.95-2.05 (m, 2H), 2.15-2.25 (m, 2H), 2.80-2.90 (m, 2H), 3.55 (s, 2H), 3.70-3.80 (m, 1H), 4.07 (s, 6H), 4.70-4.80 (m, 1H), 4.47 (s, 1H), 7.19 (d, J=9.2 Hz, 1H), 7.30-7.34 (m, 5H), 7.40 (d, J=8.8 Hz, 2H), −7.55 (s, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 514 (M⁺+1)

Example 592 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(1-piperidinyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (40 mg, yield 56%).

¹H-NMR (CDCl₃, 400 MHz): 1.60-1.85 (m, 6H), 2.33-2.46 (m, 2H), 3.15-3.25 (m, 2H), 4.057 (s, 3H), 4.059 (s, 3H), 5.33 (s, 1H), 6.45 (d, J=5.4 Hz, 1H), 7.14 (d, J=9.0 Hz, 2H), 7.45 (s, 1H), 7.57-7.62 (m, 3H), 8.23 (s, 1H), 8.47 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 423 (M⁺+1)

Example 593 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(1-piperidinyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (40 mg, yield 58%).

¹H-NMR (CDCl₃, 400 MHz): 1.50-1.90 (m, 6H), 2.12 (s, 3H), 2.25 (s, 3H), 2.35-2.50 (m, 2H), 3.15-3.25 (m, 2H), 4.07 (s, 3H), 4.08 (s, 3H), 5.41 (s, 1H), 6.30 (d, J=5.6 Hz, 1H), 7.00 (d, J=8.8 Hz, 1H), 7.53 (s, 1H), 7.64 (s, 1H), 7.84 (d, J=8.8 Hz, 1H), 8.25 (s, 1H), 8.43 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 451 (M⁺+1)

Example 594 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-nitrophenyl}-N′-(1-piperidinyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-nitroaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (35 mg, yield 51%).

¹H-NMR (CDCl₃, 400 MHz): 1.60-1.85 (m, 6H), 2.43-2.48 (m, 2H), 3.15-3.25 (m, 2H), 4.09 (s, 3H), 4.12 (s, 3H), 5.63 (s, 1H), 6.59 (d, J=5.6 Hz, 1H), 7.47-7.52 (m, 1H), 7.57 (s, 1H), 7.82 (m, 1H), 8.12 (d, J=2.9 Hz, 1H), 9.00 (d, J=9.3 Hz, 1H), 11.42 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 595 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-chlorophenyl}-N′-(1-piperidinyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-chloroaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (38 mg, yield 55%).

¹H-NMR (CDCl₃, 400 MHz): 1.60-1.85 (m, 6H), 2.35-2.50 (m, 2H), 3.15-3.25 (m, 2H), 4.07 (s, 6H), 5.45-5.50 (m, 1H), 7.15-7.19 (m, 1H), 7.34-7.36 (m, 2H), 7.53 (s, 1H), 8.44-8.47 (m, 1H), 8.63 (d, J=1.2 Hz, 1H), 9.04 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 596 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-methoxyphenyl}-N′-(1-piperidinyl)urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (45 mg, yield 65%).

¹H-NMR (CDCl₃, 400 MHz): 1.60-1.85 (m, 6H), 2.30-2.45 (m, 2H), 3.10-3.20 (m, 2H), 3.91 (s, 3H), 4.07 (s, 6H), 5.30-5.40 (m, 1H), 6.79 (d, J=2.4 Hz, 1H), 6.82-6.86 (m, 1H), 7.33 (d, J=2.2 Hz, 1H), 7.57 (d, J=1.0 Hz, 1H), 8.33 (dd, J=1.2 Hz, J=8.5 Hz, 1H), 8.63 (d, J=1.5 Hz, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 454 (M⁺+1)

Example 597 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-nitrophenyl}-N′-(1-piperidinyl)urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (50 mg, yield 73%).

¹H-NMR (CDCl₃, 400 MHz): 1.50-2.00 (m, 6H), 2.38-2.48 (m, 2H), 3.15-3.20 (m, 2H), 4.08 (s, 3H), 4.09 (s, 3H), 5.57 (s, 1H), 7.36 (s, 1H), 7.53-7.57 (m, 2H), 8.17 (d, J=2.9 Hz, 1H), 8.61 (s, 1H), 8.93 (d, J=9.3 Hz, 1H), 11.41 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 469 (M⁺+1)

Example 598 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyphenyl}-N′-1′-piperidinyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (43 mg, yield 62%).

¹H-NMR (CDCl₃, 400 MHz): 1.50-1.80 (m, 6H), 2.30-2.45 (m, 2H), 3.15-3.25 (m, 2H), 3.89 (s, 3H), 4.07 (s, 6H), 5.33 (s, 1H), 6.50 (d, J=5.6 Hz, 1H), 6.72 (d, J=2.4 Hz, 1H), 6.80 (dd, J=2.4 Hz, J=8.8 Hz, 1H), 7.52 (s, 1H), 7.59 (s, 1H), 8.32 (d, J=8.8 Hz, 1H), 8.47 (d, J=5.4 Hz, 1H), 8.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 453 (M⁺+1)

Example 599 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-methoxyphenyl}-N′-(1-morphonyl)urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminomorpholine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (26 mg, yield 37%).

¹H-NMR (CDCl₃, 400 MHz): 2.60-2.75 (m, 2H), 2.90-3.10 (m, 2H), 3.40-3.55 (m, 2H), 3.65-3.80 (m, 2H), 3.91 (s, 3H), 4.07 (s, 3H), 4.08 (s, 3H), 5.45 (s, 1H), 6.80 (d, J=2.7 Hz, 1H), 6.85 (dd, J=2.4 Hz, J=8.8 Hz, 1H), 7.34 (s, 1H), 7.56 (s, 1H), 8.33 (d, J=8.8 Hz, 1H), 8.63 (s, 1H), 8.73 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 456 (M⁺+1)

Example 600 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyphenyl}-N′-(1-homopiperidinyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminohomopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (35 mg, yield 49%).

¹H-NMR (CDCl₃, 400 MHz): 1.50-1.90 (m, 8H), 2.85-3.00 (m, 2H), 3.05-3.20 (m, 2H), 3.90 (s, 3H), 4.07 (s, 3H), 4.08 (s, 3H), 5.66 (s, 1H), 6.75-6.90 (m, 2H), 7.32 (s, 1H), 7.57 (s, 1H), 8.35 (d, J=8.5 Hz, 1H), 8.63 (s, 1H), 8.95 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 601 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(1-morphonyl)urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminomorpholine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (47 mg, yield 66%).

¹H-NMR (CDCl₃, 400 MHz): 2.50-2.70 (m, 2H), 2.90-3.10 (m, 2H), 3.65-3.85 (m, 2H), 3.85-4.00 (m, 2H), 4.07 (s, 3H), 4.08 (s, 3H), 5.45 (s, 1H), 7.21 (d, J=9.0 Hz, 2H), 7.33 (s, 1H), 7.56 (s, 1H), 7.60 (d, J=9.0 Hz, 2H), 8.12 (s, 1H), 8.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 426 (M⁺+1)

Example 602 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(1-homopiperidinyl)urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminohomopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (48 mg, yield 65%).

¹H-NMR (CDCl₃, 400 MHz): 1.55-1.85 (m, 8H), 2.85-3.00 (m, 2H), 3.05-3.20 (m, 2H), 4.07 (s, 3H), 4.08 (s, 3H), 5.67 (s, 1H), 7.19 (d, J=9.0 Hz, 2H), 7.33 (s, 1H), 7.57 (s, 1H), 7.60 (d, J=8.8 Hz, 2H), 8.33 (s, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 438 (M⁺+1)

Example 603 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(1-piperidinyl)urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (47 mg, yield 66%).

¹H-NMR (CDCl₃, 400 MHz): 1.50-1.80 (m, 6H), 2.30-2.45 (m, 2H), 3.10-3.20 (m, 2H), 4.07 (s, 3H), 4.08 (s, 3H), 5.40-5.50 (m, 1H), 7.19 (d, J=8.8 Hz, 2H), 7.35 (s, 1H), 7.57 (s, 1H), 7.59 (d, J=8.8 Hz, 2H), 8.25 (s, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 424 (M⁺+1)

Example 604 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-[4-(N-benzyl)piperidinyl]urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-amino-1-benzylpiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (45 mg, yield 55%).

¹H-NMR (CDCl₃, 400 MHz): 2.07-2.18 (m, 4H), 2.24 (s, 3H), 2.40-2.54 (m, 1H), 2.80-2.95 (m, 1H), 3.25-3.30 (m, 1H), 3.45-3.60 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 4.09 (d, J=12.7 Hz, 1H), 4.14 (d, J=12.7 Hz, 1H), 4.60 (s, 1H), 6.30 (d, J=5.4 Hz, 1H), 6.90-7.00 (m, 2H), 7.10-7.54 (m, 7H), 7.61 (s, 1H), 8.63 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 527 (M⁺+1)

Example 605 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-chlorophenyl}-N′-[4-(N-benzyl)piperidinyl]urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-chloroaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-amino-1-benzylpiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (35 mg, yield 43%).

¹H-NMR (CDCl₃, 400 MHz): 1.73-1.80 (m, 2H), 2.25-2.40 (m, 2H), 2.56-2.63 (m, 1H), 2.71-2.76 (m, 1H), 2.98-3.00 (m, 1H), 3.62 (d, J=12.7 Hz, 1H), 3.66 (d, J=12.9 Hz, 1H), 4.07 (s, 6H), 4.30-4.40 (m, 1H), 5.30 (br, 1H), 7.14-7.18 (m, 1H), 7.30-7.33 (m, 7H), 7.52 (s, 1H), 8.17-8.22 (m, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 606 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-nitrophenyl}-N′-[4-(N-benzyl)piperidinyl]urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-amino-1-benzylpiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (45 mg, yield 57%).

¹H-NMR (CDCl₃, 400 MHz): 1.75-1.80 (m, 2H), 2.32-2.43 (m, 2H), 2.62-2.68 (m, 1H), 2.73-2.78 (m, 1H), 2.95-3.01 (m, 1H), 3.68 (s, 2H), 4.07 (s, 3H), 4.08 (s, 3H), 4.41 (s, 1H), 5.48 (s, 1H), 7.27-7.36 (m, 6H), 7.50-7.55 (m, 2H), 8.13 (d, J=2.7 Hz, 1H), 8.60 (s, 1H), 8.77 (d, J=9.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 545 (M⁺+1)

Example 607 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyphenyl}-N′-[4-(N-benzyl)piperidinyl]urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 4-amino-1-benzylpiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (55 mg, yield 68%).

¹H-NMR (CDCl₃, 400 MHz): 1.80-1.90 (m, 1H), 2.35-2.50 (m, 2H), 2.70-2.75 (m, 1H), 2.88-2.93 (m, 1H), 3.09-3.16 (m, 1H), 3.23-3.31 (m, 1H), 3.75 (d, J=12.9 Hz, 1H), 3.79 (d, J=12.9 Hz, 1H), 3.84 (s, 3H), 4.07 (s, 6H), 4.45-4.55 (m, 1H), 5.67 (d, J=7.6 Hz, 1H), 6.77 (d, J=2.4 Hz, 1H), 6.82 (dd, J=2.4 Hz, J=8.8 Hz, 1H), 6.92 (s, 1H), 7.30-7.40 (m, 5H), 7.55 (s, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 530 (M⁺+1)

Example 608 N-{4-[(6,7-Dimethoxy-4-quinolyl)-oxy]phenyl}-N′-(1-homopiperidinyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminohomopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (35 mg, yield 47%).

¹H-NMR (CDCl₃, 400 MHz): ¹H-NMR (CDCl₃, 400 MHz): 1.50-1.80 (m, 8H), 2.85-3.00 (m, 2H), 3.10-3.20 (m, 2H), 4.055 (s, 3H), 4.059 (s, 3H), 5.66 (s, 1H), 6.45 (d, J=5.4 Hz, 1H), 7.14 (d, J=6.8 Hz, 2H), 7.44 (s, 1H), 7.58 (s, 1H), 7.59 (d, J=6.8 Hz, 2H), 8.32 (s, 1H), 8.47 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 437 (M⁺+1)

Example 609 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(1-homopiperidinyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminohomopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (43 mg, yield 55%).

¹H-NMR (CDCl₃, 400 MHz): 1.55-1.85 (m, 8H), 2.85-3.00 (m, 2H), 3.10-3.20 (m, 2H), 4.07 (s, 3H), 4.09 (s, 3H), 5.80 (s, 1H), 6.55 (d, J=5.6 Hz, 1H), 6.98-7.03 (m, 2H), 7.55 (s, 1H), 7.65 (s, 1H), 8.37-8.43 (m, 1H), 8.50 (d, J=5.9 Hz, 1H), 8.65-8.70 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 491 (M⁺+1)

Example 610 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(1-pyrrolidinyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminopyrrolidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (47 mg, yield 69%).

¹H-NMR (CDCl₃, 400 MHz): 1.86-2.00 (m, 4H), 2.50-2.70 (m, 2H), 2.85-3.05 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 6.05 (s, 1H), 6.50 (d, J=5.4 Hz, 1H), 6.95-7.05 (m, 2H), 7.45 (s, 1H), 7.53 (s, 1H), 8.30-8.35 (m, 1H), 8.45-8.55 (m, 2H)

Mass spectrometry value (ESI-MS, m/z): 463 (M⁺+1)

Example 611 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(methylamino)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, methylhydrazine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (47 mg, yield 76%).

¹H-NMR (CDCl₃, 400 MHz): 3.18 (s, 3H), 4.06 (s, 3H), 4.08 (s, 3H), 6.55 (d, J=8.5 Hz, 1H), 7.53 (s, 1H), 7.60 (s, 1H), 8.05 (s, 1H), 8.37 (t, J=9.3 Hz, 1H), 8.49 (d, J=5.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 423 (M⁺+1)

Example 612 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(phenylamino)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, phenylhydrazine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (47 mg, yield 66%).

¹H-NMR (CDCl₃, 400 MHz): 4.06 (s, 3H), 4.08 (s, 3H), 5.95 (s, 1H), 6.36 (s, 1H), 6.55 (d, J=5.6 Hz, 1H), 6.94-7.07 (m, 5H), 7.30-7.36 (m, 2H), 7.53 (s, 1H), 7.62 (s, 1H), 8.15-8.20 (m, 1H), 8.38 (d, J=9.0 Hz, 1H), 8.49 (d, J=5.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 485 (M⁺+1)

Example 613 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(1′-piperidinyl]urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (50 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-aminopiperidine (50 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to the reaction solution to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (43 mg, yield 61%)

¹H-NMR (CDCl₃, 400 MHz): 1.60-1.90 (m, 6H), 2.35-2.50 (m, 2H), 3.15-3.25 (m, 2H), 4.06 (s, 3H), 4.08 (s, 3H), 5.49 (s, 1H), 6.54 (d, J=5.6 Hz, 1H), 6.96-7.03 (m, 2H), 7.55 (s, 1H), 7.61 (s, 1H), 8.35-8.40 (m, 1H), 8.50 (d, J=5.6 Hz, 1H), 8.53-8.56 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 477 (M⁺+1)

Example 614 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-methylbenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml), and ethanol (1 ml) to prepare a solution. Commercially available 2-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added thereto, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (78 mg, yield 97%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.17 (s, 3H), 4.09 (s, 3H), 4.13 (s, 3H), 6.69 (d, J=5.86 Hz, 1H), 7.26-7.36 (m, 5H), 7.47-7.49 (m, 1H), 7.58 (d, J=8.05 Hz, 1H), 7.61 (s, 1H), 7.88 (bs, 1H), 7.94 (d, J=9.03 Hz, 2H), 8.52 (d, J=5.86 Hz, 1H), 8.89 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 615 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(2-phenylacetyl)thiourea

According to the descrition of technical literature, commercially available 2-phenylethanoyl chloride (80 mg) was dissolved in acetonitrile (20 ml). Potassium thiocyanate (300 mg) was added to the solution, and the mixture was heated at 80° C. for 2 hr. Water was added to the reaction solution, and the organic layer was extracted and was concentrated to give 2-phenylethanoyl isothiocyanate. 2-Phenylethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (66 mg, yield 85%) (Referenc: Elmore, D. T. et al., Journal of chemical Society 1956, 4458).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.84 (s, 2H), 3.94 (s, 3H), 3.95 (s, 3H), 6.50 (d, J=5.37 Hz, 1H), 7.27-7.55 (m, 9H), 8.01 (dd, J=2.07 Hz, J=12.32 Hz, 1H), 8.51 (d, J=5.37 Hz, 1H), 11.82 (s, 1H), 2.49 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

In the following examples, when carbonyl isothiocyanate is used, except for the case where the carbonyl isothiocyanate is purchasable, this compound was prepared from a fatty acid or an acid chloride by the method described in Example 615 according to the method of the literature and was used in the reaction without isolation and purification

Example 616 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-(2-morpholinoethyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was dissolved in chloroform (5 ml), and triethylamine (0.5 ml) to prepare a solution. A solution of triphosgene (68 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-morpholino-1-ethanamine (30 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (70 mg, yield 84%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.15 (s, 3H), 2.26 (s, 3H), 2.47 (s, 4H), 2.52-2.55 (m, 2H), 3.38-3.42 (m, 2H), 3.63-3.66 (m, 4H), 4.05 (s, 3H), 4.07 (s, 3H), 5.43-5.45 (m, 1H), 6.30 (d, J=5.4 Hz, 1H), 6.49 (s, 1H), 6.97 (s, 1H), 7.43 (s, 1H), 7.47 (s, 1H), 7.59 (s, 1H), 8.45 (d, J=5.1 Hz, 1H)

Example 617 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(2-morpholinoethyl)urea

4-[(6,7-Dimethyl-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was dissolved in chloroform (5 ml), and triethylamine (0.5 ml) to prepare a solution. A solution of triphosgene (68 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-morpholino-1-ethanamine (30 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (90 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.14 (s, 3H), 2.28 (s, 3H), 2.48-2.53 (m, 6H), 3.24-3.41 (m, 2H), 3.62-3.64 (m, 4H), 4.06 (s, 3H), 4.07 (s, 3H), 5.31-5.32 (m, 1H), 6.26 (d, J=5.4 Hz, 1H), 6.49 (s, 1H), 7.01 (d, J=8.5 Hz, 1H), 7.32 (d, J=8.5 Hz, 1H), 7.44 (s, 1H), 7.61 (s, 1H), 8.45 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 618 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-tetrahydro-1H-1-pyrrolylethyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in chloroform (5 ml), and triethylamine (0.5 ml) to prepare a solution. A solution of triphosgene (77 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-tetrahydro-1H-1-pyrrolyl-1-ethanamine (30 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (40 mg, yield 46%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.82-1.90 (m, 4H), 2.68-2.85 (m, 6H), 3.38-3.46 (m, 2H), 4.05 (s, 6H), 5.35 (s, 1H), 5.97 (s, 1H), 6.44 (d, J=5.4 Hz, 1H), 7.09 (d, J=8.8 Hz, 2H), 7.41 (s, 1H), 7.48 (d, J=8.8 Hz, 2H), 7.57 (s, 1H), 8.46 (d, J=5.4 Hz, 1H)

Example 619 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-(2-tetrahydro-1H-1-pyrrolylethyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was dissolved in chloroform (5 ml), and triethylamine (0.5 ml) to prepare a solution. A solution of triphosgene (68 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-tetrahydro-1H-1-pyrrolyl-1-ethanamine (26 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (26 mg, yield 32%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.86 (s, 4H), 2.13 (s, 3H), 2.26 (s, 3H), 2.70-2.77 (m, 4H), 2.81 (t, J=5.6 Hz, 2H), 3.45-3.49 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 5.89 (s, 1H), 6.30 (d, J=5.1 Hz, 1H), 6.93 (s, 1H), 7.42 (s, 1H), 7.55 (s, 1H), 7.59 (s, 1H), 8.44 (d, J=5.1 Hz, 1H)

Example 620 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(2-tetrahydro-1H-1-pyrrolylethyl)urea

4-[(6,7-Dimethyl-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was dissolved in chloroform (5 ml), and triethylamine (0.5 ml) to prepare a solution. A solution of triphosgene (68 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-tetrahydro-1H-1-pyrrolyl-1-ethanamine (26 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (21 mg, yield 26%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.86 (s, 4H), 2.11 (s, 3H), 2.27 (s, 3H), 2.76 (s, 4H), 2.82 (t, J=5.6 Hz, 2H), 3.42-3.49 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 5.86 (s, 1H), 6.27 (d, J=5.1 Hz, 1H), 6.97 (d, J=8.8 Hz, 1H), 7.39 (d, J=8.8 Hz, 1H), 7.43 (s, 1H), 7.61 (s, 1H), 8.43 (d, J=5.1 Hz, 1H)

Example 621 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-tetrahydro-1H-1-pyrrolylethyl)urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in chloroform (5 ml), and triethylamine (0.5 ml) to prepare a solution. A solution of triphosgene (77 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-tetrahydro-1H-1-pyrrolyl-1-ethanamine (30 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (8 mg, yield 9%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.86 (s, 4H), 2.72-2.92 (m, 6H), 3.39-3.45 (m, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 5.42 (s, 1H), 7.16 (d, J=9.0 Hz, 2H), 7.31 (s, 1H), 7.48 (d, J=8.8 Hz, 2H), 7.56 (s, 1H), 8.61 (s, 1H)

Example 622 N-[2-(Diethylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in chloroform (5 ml), and triethylamine (0.5 ml) to prepare a solution. A solution of triphosgene (77 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diethyl-1,2-ethanediamine (30 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (10 mg, yield 13%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.12 (t, J=7.1 Hz, 6H), 2.66-2.71 (m, 6H), 3.35-3.36 (m, 2H), 4.05 (s, 6H), 6.46 (d, J=5.4 Hz, 1H), 7.10-7.13 (m, 2H), 7.42 (s, 1H), 7.45 (d, J=9.0 Hz, 2H), 7.57 (s, 1H), 8.47 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 439 (M⁺+1)

Example 623 N-[2-(Diethylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was dissolved in chloroform (5 ml), and triethylamine (0.5 ml) to prepare a solution. A solution of triphosgene (68 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diethyl-1,2-ethanediamine (27 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (7 mg, yield 10%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.12 (t, J=7.1 Hz, 6H), 2.13 (s, 3H), 2.27 (s, 3H), 2.70-2.77 (m, 6H), 3.43-3.45 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 6.30 (d, J=5.4 Hz, 1H), 6.95 (s, 1H), 7.42 (s, 1H), 7.49 (s, 1H), 7.59 (s, 1H), 8.44 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 624 N-[2-(Diethylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}urea

4-[(6,7-Dimethyl-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was dissolved in chloroform (5 ml), and triethylamine (0.5 ml) to prepare a solution. A solution of triphosgene (68 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diethyl-1,2-ethanediamine (27 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (8 mg, yield 11%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.03 (t, J=7.1 Hz, 6H), 2.12 (s, 3H), 2.28 (s, 3H), 2.58-2.67 (m, 6H), 3.35-3.38 (m, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 6.26 (d, J=5.4 Hz, 1H), 6.98 (d, J=8.8 Hz, 1H), 7.32 (d, J=8.8 Hz, 1H), 7.43 (s, 1H), 7.61 (s, 1H), 8.43 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 625 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-[2-(dimethylamino)ethyl]urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was dissolved in chloroform (5 ml), and triethylamine (0.5 ml) to prepare a solution. A solution of triphosgene (68 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-dimethyl-1,2-ethanediamine (20 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (24 mg, yield 36%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.03 (s, 3H), 2.13 (s, 3H), 2.25 (s, 3H), 2.28 (s, 3H), 2.51 (s, 2H), 3.38-3.39 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 5.59 (s, 1H), 6.30 (d, J=4.9 Hz, 1H), 6.94 (s, 1H), 7.42 (s, 1H), 7.55 (s, 1H), 7.59 (s, 1H), 8.44 (d, J=5.1 Hz, 1H)

Example 626 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-[2-(dimethylamino)ethyl]urea

4-[(6,7-Dimethyl-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was dissolved in chloroform (5 ml), and triethylamine (0.5 ml) to prepare a solution. A solution of triphosgene (68 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-dimethyl-1,2-ethanediamine (20 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (18 mg, yield 28%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.02 (s, 3H), 2.12 (s, 3H), 2.26 (s, 6H), 2.44-2.51 (m, 2H), 3.37-3.38 (m, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 5.45 (s, 1H), 6.26 (d, J=5.1 Hz, 1H), 6.99 (d, J=8.8 Hz, 1H), 7.38 (d, J=8.3 Hz, 1H), 7.43 (s, 1H), 7.61 (s, 1H), 8.44 (d, J=5.1 Hz, 1H)

Example 627 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[2-(dimethylamino)ethyl]urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in chloroform (5 ml), and triethylamine (0.5 ml) to prepare a solution. A solution of triphosgene (77 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-dimethyl-1,2-ethanediamine (23 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (14 mg, yield 21%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.27 (s, 3H), 2.34 (s, 3H), 2.46-2.49 (m, 2H), 3.31-3.35 (m, 2H), 4.07 (s, 6H), 5.14 (s, 1H), 5.59 (s, 1H), 7.16 (d, J=8.3 Hz, 2H), 7.31 (s, 1H), 7.47 (d, J=8.5 Hz, 2H), 7.56 (s, 1H), 8.61 (s, 1H)

Example 628 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-morpholinoethyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (100 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-morpholino-1-ethanamine (66 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (162 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.46-2.48 (m, 4H), 2.54 (t, J=5.9 Hz, 2H), 3.40 (q, J=5.4 Hz, 2H), 3.64 (t, J=4.6 Hz, 4H), 4.03 (s, 3H), 4.05 (s, 3H), 5.59 (s, 1H), 6.45 (d, J=5.4 Hz, 1H), 7.12 (d, J=8.8 Hz, 2H), 7.41 (s, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.57 (s, 1H), 8.47 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 453 (M⁺+1)

Example 629 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-morpholinoethyl)urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (100 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-morpholino-1-ethanamine (66 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (41 mg, yield 27%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.45 (t, J=4.1 Hz, 4H), 2.51 (t, J=5.6 Hz, 2H), 3.38 (q, J=5.6 Hz, 2H), 3.63 (t, J=4.6 Hz, 4H), 4.06 (s, 3H), 4.07 (s, 3H), 5.66 (t, J=5.1 Hz, 1H), 7.17 (d, J=8.8 Hz, 2H), 7.31 (s, 1H), 7.44 (d, J=8.8 Hz, 2H), 7.55 (s, 1H), 7.64 (s, 1H), 8.60 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 454 (M⁺+1)

Example 630 N-[2-(Diethylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-methoxyphenyl}urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (140 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diethyl-1,2-ethanediamine (55 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (83 mg, yield 57%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.39 (t, J=7.3 Hz, 6H), 3.11-3.20 (m, 6H), 3.65-3.68 (m, 2H), 3.85 (s, 3H), 4.065 (s, 3H), 4.067 (s, 3H), 6.77-6.82 (m, 2H), 7.30 (s, 1H), 7.54 (s, 1H), 7.62 (s, 1H), 8.16 (d, J=8.8 Hz, 1H), 8.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 470 (M⁺+1)

Example 631 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-methoxyphenyl}-N′-(2-morpholinoethyl)urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (140 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-morpholino-1-ethanamine (61 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (165 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.49-2.57 (m, 6H), 3.39-3.43 (m, 2H), 3.70-3.73 (m, 4H), 3.84 (s, 3H), 4.068 (s, 3H), 4.072 (s, 3H), 5.53 (s, 1H), 6.79-6.86 (m, 2H), 6.97-6.98 (m, 1H), 7.33 (s, 1H), 7.55 (s, 1H), 8.14 (d, J=8.8 Hz, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 484 (M⁺+1)

Example 632 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-methoxyphenyl}-N′-(2-tetrahydro-1H-1-pyrrolylethyl)urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (140 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-tetrahydro-1H-1-pyrrolyl-1-ethanamine (54 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (26 mg, yield 18%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.16-2.19 (m, 4H), 3.08-3.14 (m, 4H), 3.31-3.34 (m, 2H), 3.70-3.74 (m, 2H), 3.87 (s, 3H), 4.065 (s, 3H), 4.068 (s, 3H), 6.76-6.81 (m, 2H), 7.31 (s, 1H), 7.36 (s, 1H), 7.55 (s, 1H), 7.59 (s, 1H), 8.19 (d, J=8.5 Hz, 1H), 8.62 (s, 1H)

Example 633 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-methoxyphenyl}-N′-[3-(4-methylpiperazino)-propyl]urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (140 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 3-(4-methylpiperazino)-1-propaneamine (74 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (62 mg, yield 39%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.70-1.75 (m, 2H), 2.29 (d, J=7.6 Hz, 3H), 2.41-2.52 (m, 10H), 3.24-3.46 (m, 2H), 3.84 (d, J=4.4 Hz, 3H), 4.07 (s, 6H), 6.77-6.85 (m, 3H), 7.32 (d, J=1.7 Hz, 1H), 7.55 (s, 1H), 8.18 (d, J=8.8 Hz, 1H), 8.63 (s, 1H)

Example 634 N-(1-Benzyl-4-piperidyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (140 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 1-benzyl-4-piperidineamine (89 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (124 mg, yield 74%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.43-1.51 (m, 2H), 1.97-1.99 (m, 4H), 2.14 (s, 3H), 2.21 (s, 3H), 2.82-2.84 (m, 2H), 3.50 (s, 2H), 4.047 (s, 3H), 4.053 (s, 3H), 4.95 (d, J=7.8 Hz, 1H), 6.30 (d, J=5.4 Hz, 1H), 6.35 (s, 1H), 6.94 (s, 1H), 7.27-7.31 (m, 5H), 7.43 (s, 1H), 7.51 (s, 1H), 7.59 (s, 1H), 8.45 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 541 (M⁺+1)

Example 635 N-(1-Benzyl-4-piperidyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}urea

4-[(6,7-Dimethyl-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 1-benzyl-4-piperidineamine (89 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (101 mg, yield 60%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.41-1.44 (m, 2H), 1.95-1.97 (m, 4H), 2.13 (s, 3H), 2.25 (s, 3H), 2.81 (d, J=11.7 Hz, 2H), 3.4.9 (s, 2H), 3.71-3.75 (m, 1H), 4.05 (s, 3H), 4.06 (s, 3H), 6.26 (d, J=5.4 Hz, 1H), 6.99 (d, J=8.5 Hz, 1H), 7.26-7.32 (m, 7H), 7.44 (s, 1H), 7.61 (s, 1H), 8.45 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 541 (M⁺+1)

Example 636 N-(1-Benzyl-4-piperidyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (151 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 1-benzyl-4-piperidineamine (97 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (142 mg, yield 81%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.41-1.51 (m, 2H), 1.94-1.96 (m, 2H), 2.07-2.16 (m, 2H), 2.79-2.82 (m, 2H), 3.48 (s, 2H), 3.68-3.75 (m, 1H), 4.05 (s, 6H), 5.09 (d, J=7.8 Hz, 1H), 7.07 (s, 1H), 7.16 (d, J=9.0 Hz, 2H), 7.26-7.31 (m, 5H), 7.40 (d, J=9.0 Hz, 2H), 7.54 (s, 1H), 8.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 514 (M⁺+1)

Example 637 N-(1-Benzyl-4-piperidyl)-N′-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}urea

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (134 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 1-benzyl-4-piperidineamine (85 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (185 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.40-1.55 (m, 2H), 1.93-1.99 (m, 2H), 2.12-2.17 (m, 2H), 2.81-2.83 (m, 2H), 3.49 (s, 2H), 3.70-3.74 (m, 1H), 4.05 (s, 3H), 4.06 (s, 3H), 5.74 (d, J=7.8 Hz, 1H), 7.13-7.16 (m, 1H), 7.23-7.32 (m, 7H), 7.51 (s, 1H), 8.29 (d, J=9.0 Hz, 1H), 8.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 548 (M⁺+1)

Example 638 N-(1-Benzyl-4-piperidyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-nitrophenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (131 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 1-benzyl-4-piperidineamine (84 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (141 mg, yield 86%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.55-1.63 (m, 2H), 1.97-2.03 (m, 4H), 2.81-2.90 (m, 2H), 3.53 (s, 2H), 3.72-3.73 (m, 1H), 4.04 (s, 3H), 4.05 (s, 3H), 5.35-5.36 (m, 1H), 6.47 (d, J=5.1 Hz, 1H), 7.26-7.50 (m, 7H), 8.01 (d, J=2.9 Hz, 1H), 8.52 (d, J=5.4 Hz, 1H), 8.77 (d, J=9.3 Hz, 1H), 9.72 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 558 (M⁺+1)

Example 639 N-(1-Benzyl-4-piperidyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (142 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 1-benzyl-4-piperidineamine (91 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (47 mg, yield 28%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.47-1.55 (m, 2H), 1.98-2.00 (m, 2H), 2.15-2.20 (m, 2H), 2.84-2.87 (m, 2H), 3.53 (s, 2H), 3.70-3.80 (m, 1H), 4.04 (s, 3H), 4.05 (s, 3H), 4.89 (d, J=7.3 Hz, 1H), 6.40 (d, J=5.1 Hz, 1H), 6.93 (s, 1H), 7.06-7.17 (m, 2H), 7.26-7.32 (m, 5H), 7.41 (s, 1H), 7.49-7.53 (m, 1H), 7.58 (s, 1H) 8.47 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 531 (M⁺+1)

Example 640 N-(1-Benzyl-4-piperidyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (131 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 1-benzyl-4-piperidineamine (89 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (151 mg, yield 93%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.54-1.63 (m, 2H), 2.01-2.03 (m, 2H), 2.16-2.21 (m, 2H), 2.87-2.90 (m, 2H), 3.54 (s, 2H), 3.72-3.73 (m, 1H), 4.07 (s, 3H), 4.08 (s, 3H), 4.97 (brs, 1H), 7.26-7.34 (m, 5H), 7.51-7.56 (m, 2H), 8.13 (d, J=2.9 Hz, 1H), 8.60 (s, 1H), 8.80 (d, J=9.5 Hz, 1H), 9.77 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 559 (M⁺+1)

Example 641 N-(1-Benzyl-4-piperidyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-methoxyphenyl}urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 1-benzyl-4-piperidineamine (89 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (118 mg, yield 71%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.47-1.54 (m, 2H), 1.98-2.01 (m, 2H), 2.13-2.19 (m, 2H), 2.83-2.86 (m, 2H), 3.52 (s, 2H), 3.70-3.73 (m, 1H), 3.85 (s, 3H), 4.07 (s, 6H), 4.66 (d, J=8.1 Hz, 1H), 6.71 (s, 1H), 6.78 (d, J=2.4 Hz, 1H), 6.82-6.85 (m, 1H), 7.26-7.52 (m, 5H), 7.55 (s, 1H), 8.10 (d, J=8.8 Hz, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 544 (M⁺+1)

Example 642 N-(1-Benzyl-4-piperidyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-methylphenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (142 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 1-benzyl-4-piperidineamine (91 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (84 mg, yield 50%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.46-1.54 (m, 2H), 1.97-2.00 (m, 2H), 2.13 (s, 3H), 2.13-2.23 (m, 2H), 2.82-2.85 (m, 2H), 3.51 (s, 2H), 3.73-3.75 (m, 1H), 4.04 (s, 3H), 4.05 (s, 3H), 4.98 (d, J=7.8 Hz, 1H), 6.27 (d, J=5.4 Hz, 1H), 6.90 (s, 1H), 7.02 (d, J=8.5 Hz, 1H), 7.18-7.21 (m, 1H), 7.25-7.31 (m, 4H), 7.36 (d, J=2.4 Hz, 1H), 7.42 (s, 1H), 7.60 (s, 1H), 8.43 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 527 (M⁺+1)

Example 643 N-(1-Benzyl-4-piperidyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methylphenyl]urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (142 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 1-benzyl-4-piperidineamine (91 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 52%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.42-1.50 (m, 2H), 1.96-1.98 (m, 2H), 2.12-2.18 (m, 2H), 2.28 (s, 3H), 2.81-2.84 (m, 2H), 3.50 (s, 2H), 3.73-3.75 (m, 1H), 4.04 (s, 3H), 4.05 (s, 3H), 4.68 (d, J=7.6 Hz, 1H), 6.15 (s, 1H), 6.49 (d, J=5.4 Hz, 1H), 7.02-7.05 (m, 2H), 7.23-7.33 (m, 4H), 7.43 (s, 1H), 7.53-7.55 (m, 2H), 8.50 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 527 (M⁺+1)

Example 644 N-(1-Benzyl-4-piperidyl)-N′-{3-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}urea

3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (134 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 1-benzyl-4-piperidineamine (86 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (112 mg, yield 68%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.44-1.53 (m, 2H), 1.96-1.98 (m, 2H), 2.12-2.17 (m, 2H), 2.80-2.83 (m, 2H), 3.49 (s, 2H), 3.72-3.74 (m, 1H), 4.03 (s, 3H), 4.04 (s, 3H), 5.18 (d, J=7.8 Hz, 1H), 6.29 (d, J=5.4 Hz, 1H), 7.12 (d, J=8.8 Hz, 1H), 7.23-7.32 (m, 5H), 7.39-7.40 (m, 2H), 7.60 (s, 1H), 7.64 (d, J=2.4 Hz, 1H), 8.44 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 547 (M⁺+1)

Example 645 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-[2-(diethylamino)ethyl]urea

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diethyl-1,2-ethanediamine (52 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (64 mg, yield 45%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.16 (t, J=7.3 Hz, 6H), 2.75-2.83 (m, 6H), 3.45-3.49 (m, 2H), 4.07 (s, 6H), 6.41 (brs, 1H), 7.14-7.17 (m, 1H), 7.28-7.32 (m, 2H), 7.51 (s, 1H), 8.20 (d, J=9.0 Hz, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 646 N-[2-(Diethylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-nitrophenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (131 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diethyl-1,2-ethanediamine (51 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (65 mg, yield 46%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.16-1.20 (m, 6H), 2.77-2.86 (m, 6H), 3.48-3.52 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 6.48 (d, J=5.4 Hz, 1H), 7.44-7.50 (m, 3H), 8.01 (d, J=2.9 Hz, 1H), 8.53 (d, J=5.1 Hz, 1H), 8.70 (d, J=9.5 Hz, 1H), 9.79 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 484 (M⁺+1)

Example 647 N-[2-(Diethylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (131 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diethyl-1,2-ethanediamine (51 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (107 mg, yield 76%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.10 (t, J=7.1 Hz, 6H), 2.67 (q, J=7.1 Hz, 4H), 2.72 (t, J=5.9 Hz, 2H), 3.40-3.44 (m, 2H), 4.075 (s, 3H), 4.079 (s, 3H), 6.07 (brs, 1H), 7.34 (s, 1H), 7.52 (s, 1H), 7.54 (dd, J=2.7, J=9.3 Hz, 1H), 8.13 (d, J=2.9 Hz, 1H), 8.61 (s, 1H), 8.78 (d, J=9.3 Hz, 1H), 9.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 485 (M⁺+1)

Example 648 N-[2-(Diethylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-methylphenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (142 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diethyl-1,2-ethanediamine (56 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 33%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.39 (t, J=7.3 Hz, 6H), 2.12 (s, 3H), 3.12-3.20 (m, 6H), 3.67-3.68 (m, 2H), 4.046 (s, 3H), 4.052 (s, 3H), 6.27 (d, J=5.4 Hz, 1H), 7.00 (d, J=8.5 Hz, 1H), 7.28 (s, 1H), 7.36-7.44 (m, 3H), 7.60 (s, 1H), 8.42 (d, J=5.4 Hz, 1H)

Example 649 N-[2-(Diethylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methylphenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (142 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diethyl-1,2-ethanediamine (56 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (49 mg, yield 34%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.32-1.36 (m, 6H), 2.35 (s, 3H), 2.99-3.14 (m, 6H), 3.62-3.66 (m, 2H), 4.04 (s, 3H), 4.05 (s, 3H), 6.49 (d, J=5.4 Hz, 1H), 6.97-7.00 (m, 2H), 7.28 (s, 1H), 7.41 (s, 1H), 7.55 (s, 1H), 7.72 (d, J=9.3 Hz, 1H), 8.47 (d, J=5.1 Hz, 1H)

Example 650 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(diethylamino)ethyl]urea

2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diethyl-1,2-ethanediamine (52 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (32 mg, yield 22%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.26 (t, J=7.1 Hz, 6H), 2.91-2.99 (m, 6H), 3.55-3.59 (m, 2H), 4.04 (s, 3H), 4.05 (s, 3H), 6.49 (d, J=5.1 Hz, 1H), 7.07-7.10 (m, 2H), 7.21 (d, J=2.7 Hz, 1H), 7.28 (s, 1H), 7.42 (s, 1H), 7.51 (s, 1H), 8.16 (d, J=9.0 Hz, 1H), 8.50 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 473 (M⁺+1)

Example 651 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(diethylamino)ethyl]urea

3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diethyl-1,2-ethanediamine (52 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (59 mg, yield 41%).

¹H-NMR (CDCl₃-d₁, 400 MHz): 11.41 (brs, 6H), 3.18-3.19 (m, 6H), 3.64-3.73 (m, 2H), 4.05 (s, 6H), 6.31 (s, 1H), 7.12 (d, J=8.3 Hz, 1H), 7.42 (s, 2H), 7.60 (s, 1H), 7.81 (s, 1H), 8.46 (s, 1H), 8.88 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 473 (M⁺+1)

Example 652 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-nitrophenyl}-N′-(2-morpholinoethyl urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (131 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-morpholino-1-ethanamine (57 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (30 mg, yield 21%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.60-2.73 (m, 4H), 3.46-3.50 (m, 2H), 3.79-3.84 (m, 4H), 4.08 (s, 6H), 7.34 (s, 1H), 7.52-7.56 (m, 2H), 8.13 (d, J=2.7 Hz, 1H), 8.61 (s, 1H), 8.78 (d, J=9.5 Hz, 1H), 9.81 (s, 1H)

Example 653 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-nitrophenyl}-N′-(2-tetrahydro-1H-1-pyrrolylethyl)urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (131 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-tetrahydro-1H-1-pyrrolyl-1-ethanamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound 42 mg, yield 30%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.90 (s, 4H), 2.74 (s, 4H), 2.82 (t, J=5.6 Hz, 2H), 3.50 (q, J=5.4 Hz, 2H), 4.075 (s, 3H), 4.078 (s, 3H), 7.34 (s, 1H), 7.52-7.55 (m, 2H), 8.12 (d, J=2.9 Hz, 1H), 8.61 (s, 1H), 8.78 (d, J=9.3 Hz, 1H), 9.82 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 483 (M⁺+1)

Example 654 N-[2-(Diisopropylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (151 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diisopropyl-1,2-ethanediamine (74 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (52 mg, yield 33%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.06 (d, J=6.3 Hz, 12H), 2.67 (t, J=4.9 Hz, 2H), 3.07-3.11 (m, 2H), 3.24-3.31 (m, 2H), 4.05 (s, 6H), 6.45 (d, J=5.4 Hz, 1H), 7.13 (d, J=8.8 Hz, 2H), 7.42-7.44 (m, 3H), 7.56 (s, 1H), 8.47 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 655 N-[2-(Diisopropylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diisopropyl-1,2-ethanediamine (68 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (46 mg, yield 30%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.01-1.15 (m, 12H), 2.12 (s, 3H), 2.28 (s, 3H), 2.62 (brs, 2H), 3.00 (brs, 2H), 3.28 (brs, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 6.25 (s, 1H), 6.99 (d, J=8.8 Hz, 1H), 7.43 (s, 1H), 7.61 (s, 1H), 8.43 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 495 (M⁺+1)

Example 656 N-[2-(Diisopropylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (151 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diisopropyl-1,2-ethanediamine (74 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (58 mg, yield 37%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.12-1.15 (m, 12H), 2.74 (brs, 2H), 3.16 (brs, 2H), 3.34 (brs, 2H), 4.067 (s, 3H), 4.073 (s, 3H), 7.19 (d, J=9.0 Hz, 1H), 7.32 (s, 1H), 7.46 (d, J=9.0 Hz, 1H), 7.56 (s, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 657 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-[2-(diisopropylamino)-ethyl]urea

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (134 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diisopropyl-1,2-ethanediamine (65 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (64 mg, yield 43%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.45-1.48 (m, 12H), 3.19-3.22 (m, 2H), 3.60-3.65 (m, 2H), 3.73-3.74 (m, 2H), 4.07 (s, 6H), 7.12-7.15 (m, 2H), 7.51 (s, 1H), 7.70 (s, 1H), 7.97 (s, 1H), 8.16 (d, J=9.0 Hz, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 658 N-[2-(Diisopropylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-nitrophenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (131 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diisopropyl-1,2-ethanediamine (63 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (103 mg, yield 70%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.33-1.37 (m, 12H), 3.04-3.07 (m, 2H), 3.45-3.51 (m, 2H), 3.61 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.49 (d, J=5.1 Hz, 1H), 7.42-7.45 (m, 2H), 7.50 (s, 1H), 8.00 (d, J=2.9 Hz, 1H), 8.52 (d, J=5.4 Hz, 1H), 8.58-8.62 (m, 1H), 9.76 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 512 (M⁺+1)

Example 659 N-[2-(Diisopropylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (131 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diisopropyl-1,2-ethanediamine (63 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (71 mg, yield 48%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.20-1.23 (m, 12H), 2.87 (s, 2H), 3.27-3.28 (m, 2H), 3.45-3.49 (m, 2H), 4.075 (s, 3H), 4.080 (s, 3H), 7.34 (s, 1H), 7.52 (s, 1H), 7.54 (d, J=2.9 Hz, 1H), 8.12 (d, J=2.7 Hz, 1H), 8.61 (s, 1H), 8.74 (d, J=9.3 Hz, 1H), 9.84 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 513 (M⁺+1)

Example 660 N-[2-(Diisopropylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-methoxyphenyl}urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diisopropyl-1,2-ethanediamine (68 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (50 mg, yield 32%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.07 (brs, 12H), 2.69 (brs, 2H), 3.10 (brs, 2H), 3.27 (brs, 2H), 3.84 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.48 (d, J=5.1 Hz, 1H), 7.72 (d, J=2.4 Hz, 1H), 6.78 (dd, J 2.7, 8.8 Hz, 1H), 7.42 (s, 1H), 7.56 (s, 1H), 8.05 (d, J=9.0 Hz, 1H), 8.48 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 661 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(ethyl-3-methylanilino)-ethyl]urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (151 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1-ethyl-N1-(3-methylphenyl)-1,2-ethanediamine (91 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (139 mg, yield 82%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.15 (t, J=7.1 Hz, 3H), 2.30 (s, 3H), 3.39 (q, J=7.1 Hz, 2H), 3.48 (s, 4H), 4.05 (s, 3H), 4.06 (s, 3H), 6.44 (d, J=5.4 Hz, 1H), 6.56 (d, J=7.1 Hz, 1H), 6.61 (s, 2H), 7.09-7.15 (m, 3H), 7.35 (d, J=8.8 Hz, 2H), 7.46 (s, 1H), 7.55 (s, 1H), 8.46 (d, J=5.4 Hz, 1H)

Example 662 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-[2-(ethyl-3-methylanilino)ethyl]-urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1-ethyl-N1-(3-methylphenyl)-1,2-ethanediamine (84 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (137 mg, yield 84%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.13 (t, J=7.1 Hz, 3H), 2.09 (s, 3H), 2.21 (s, 3H), 2.30 (s, 3H), 3.37 (q, J=6.8 Hz, 2H), 3.46 (s, 4H), 4.06 (s, 6H), 4.84 (s, 1H), 5.92 (s, 1H), 6.27 (d, J=5.1 Hz, 1H), 6.53-6.57 (m, 3H), 6.95 (s, 1H), 7.09-7.13 (m, 1H), 7.31 (s, 1H), 7.45 (s, 1H), 7.57 (s, 1H), 8.44 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 663 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-[2-(ethyl-3-methylanilino)ethyl]-urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1-ethyl-N1-(3-methylphenyl)-1,2-ethanediamine (84 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (112 mg, yield 68%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.12 (t, J=7.1 Hz, 3H), 2.10 (s, 3H), 2.24 (s, 3H), 2.30 (s, 3H), 3.35 (q, J=6.8 Hz, 2H), 3.45 (s, 4H), 4.07 (s, 6H), 6.57 (s, 1H), 6.95 (d, J=8.5 Hz, 1H), 7.60 (s, 1H), 8.43 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 664 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-[2-(ethyl-3-methylanilino)ethyl]-urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (151 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1-ethyl-N1-(3-methylphenyl)-1,2-ethanediamine (91 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (177 mg, yield 100%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.07-1.16 (m, 3H), 2.31 (s, 3H), 3.39-3.48 (m, 6H), 4.07 (s, 6H), 7.16-7.19 (m, 3H), 7.32-7.35 (m, 2H), 7.55 (s, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 665 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-[2-(ethyl-3-methylanilino)-ethyl]urea

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (134 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1-ethyl-N1-(3-methylphenyl)-1,2-ethanediamine (80 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (146 mg, yield 91%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.09-1.17 (m, 3H), 2.31 (s, 3H), 3.41-3.50 (m, 6H), 4.07 (s, 6H), 6.60 (s, 1H), 7.31-7.33 (m, 2H), 7.52 (s, 1H), 8.18 (d, J=9.0 Hz, 1H), 8.63 (s, 1H)

Example 666 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-nitrophenyl}-N′-[2-(ethyl-3-methylanilino)ethyl]urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (131 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1-ethyl-N1-(3-methylphenyl)-1,2-ethanediamine (78 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (101 mg, yield 64%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.17 (t, J=7.1 Hz, 3H), 2.31 (s, 3H), 3.39-3.44 (q, J=7.1 Hz, 2H), 3.52 (s, 4H), 4.05 (s, 3H), 4.07 (s, 3H), 6.49 (d, J=5.4 Hz, 1H), 6.58-6.62 (m, 2H), 7.12-7.14 (m, 1H), 7.47-7.51 (m, 3H), 8.04 (d, J=2.9 Hz, 1H), 8.53 (d, J=5.4 Hz, 1H), 8.78 (d, J=9.5 Hz, 1H), 9.68 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 546 (M⁺+1)

Example 667 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-nitrophenyl}-N′-[2-(ethyl-3-methylanilino)ethyl]-urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (131 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1-ethyl-N1-(3-methylphenyl)-1,2-ethanediamine (78 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (110 mg, yield 69%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.07-1.19 (m, 3H), 2.30-2.31 (m, 3H), 3.36-3.42 (m, 2H), 3.52 (s, 4H), 4.078 (s, 3H), 4.083 (s, 3H), 6.57-6.61 (m, 4H), 7.35 (s, 1H), 7.52-7.57 (m, 2H), 8.14 (d, J=2.9 Hz, 1H), 8.61 (s, 1H), 8.80 (d, J=9.8 Hz, 1H), 9.74 (s, 1H)

Example 668 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-methoxyphenyl}-N′-[2-(ethyl-3-methylanilino)-ethyl]urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1-ethyl-N1-(3-methylphenyl)-1,2-ethanediamine (84 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reactions and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (140 mg, yield 85%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.16 (t, J=7.1 Hz, 3H), 2.31 (s, 3H), 3.40 (q, J=7.1 Hz, 2H), 3.48 (s, 4H), 3.83 (s, 3H), 4.07 (s, 6H), 6.55-6.65 (m, 2H), 6.78 (d, J=2.4 Hz, 1H), 6.83 (dd, J=2.4, 8.8 Hz, 1H), 7.13 (s, 1H), 7.33 (s, 1H), 7.55 (s, 1H), 8.07 (d, J=8.5 Hz, 1H), 8.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 532 (M⁺+1)

Example 669 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(ethyl-3-methylanilino)-ethyl]urea

2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (134 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1-ethyl-N1-(3-methylphenyl)-1,2-ethanediamine (80 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (100 mg, yield 62%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.16 (t, J=7.1 Hz, 3H), 2.30 (s, 3H), 3.40 (q, J=7.1 Hz, 2H), 3.50 (s, 4H), 4.045 (s, 3H), 4.054 (s, 3H), 6.49 (d, J=5.1 Hz, 1H), 6.56 (d, J=7.6 Hz, 1H), 6.60 (s, 1H), 7.04 (d, J=5.1 Hz, 1H), 7.09-7.13 (m, 1H), 7.21 (d, J=2.7 Hz, 1H), 7.43 (d, J=11.5 Hz, 2H), 7.51 (s, 1H), 8.19-8.22 (m, 1H), 8.50 (d, J=5.1 Hz, 1H), 8.57 (d, J=4.9 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 535 (M⁺+1)

Example 670 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyphenyl}-N′-[2-(ethyl-3-methylanilino)ethyl]urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1-ethyl-N1-(3-methylphenyl)-1,2-ethanediamine (84 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (130 mg, yield 79%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.16 (t, J=7.1 Hz, 3H), 2.30 (s, 3H), 3.40 (q, J=7.1 Hz, 2H), 3.49 (s, 4H), 3.81 (s, 3H), 4.06 (s, 6H), 6.48 (d, J=5.4 Hz, 1H), 6.55 (d, J=7.3 Hz, 1H), 6.60 (s, 1H), 6.70 (d, J=2.4 Hz, 1H), 6.79 (dd, J=2.4, 8.8 Hz, 1H), 7.11-7.15 (m, 1H), 7.45 (s, 1H), 7.56 (s, 1H), 8.10 (d, J=8.3 Hz, 1H), 8.48 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 531 (M⁺+1)

Example 671 N-[2-(Diisopropylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diisopropyl-1,2-ethanediamine (68 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (63 mg, yield 41%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.00 (brs, 12H), 2.13 (s, 3H), 2.27 (s, 3H), 2.63 (brs, 2H), 3.02 (brs, 2H), 3.27 (brs, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 6.29 (d, J=5.1 Hz, 1H), 6.98 (s, 1H), 7.43 (s, 1H), 7.59 (s, 1H), 8.44 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 495 (M⁺+1)

Example 672 N-[2-(Diisopropylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methoxyphenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-diisopropyl-1,2-ethanediamine (68 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 52%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.02-1.15 (m, 12H), 3.03 (brs, 2H), 3.26 (brs, 2H), 3.48-3.50 (m, 2H), 3.86 (s, 3H), 4.07 (s, 3H), 6.79-6.84 (m, 3H), 7.32 (s, 1H), 7.55 (s, 1H), 8.07 (s, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 498 (M⁺+1)

Example 673 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-piperidinoethyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (151 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-piperidino-1-ethanamine (65 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (119 mg, yield 78%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.51-1.70 (m, 6H), 2.44-2.65 (m, 6H), 3.41-3.45 (m, 2H), 4.04 (s, 6H), 6.45 (d, J=5.4 Hz, 1H), 7.11 (d, J=8.8 Hz, 2H), 7.27 (s, 1H), 7.41 (s, 1H), 7.49 (d, J=8.8 Hz, 2H), 7.56 (s, 1H), 8.46 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 451 (M⁺+1)

Example 674 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-(2-piperidinoethyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-piperidino-1-ethanamine (60 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (123 mg, yield 83%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.57-1.63 (m, 6H) 2.14 (s, 3H), 2.27 (s, 3H), 2.50-2.59 (m, 6H), 3.40-3.44 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 5.80 (s, 1H), 6.31 (d, J=5.1 Hz, 1H), 6.96 (s, 1H), 7.27 (s, 1H), 7.42 (s, 1H), 7.49 (s, 1H), 7.59 (s, 1H), 8.44 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 479 (M⁺+1)

Example 675 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(2-piperidinoethyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-piperidino-1-ethanamine (60 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (48 mg, yield 32%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.00 (brs, 6H), 2.09 (s, 3H), 2.30 (s, 3H), 3.08-3.18 (m, 6H), 3.70-3.74 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 6.29 (d, J=5.1 Hz, 1H), 6.94 (d, J=8.8 Hz, 1H), 7.28 (s, 1H), 7.43 (s, 1H), 7.52 (d, J=8.8 Hz, 1H), 7.62 (s, 1H), 8.42 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 479 (M⁺+1)

Example 676 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-piperidinoethyl)urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (151 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-piperidino-1-ethanamine (65 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (84 mg, yield 55%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.03 (brs, 6H), 3.09-3.18 (m, 6H), 3.66-3.76 (m, 2H), 4.060 (s, 3H), 4.063 (s, 3H), 6.73 (brs, 1H), 7.13 (d, J=8.8 Hz, 2H), 7.30 (s, 1H), 7.35 (brs, 1H), 7.54 (s, 1H), 7.59 (d, J=8.8 Hz, 2H), 8.58 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 452 (M⁺+1)

Example 677 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-(2-piperidinoethyl)urea

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (134 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-piperidino-1-ethanamine (58 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (118 mg, yield 81%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.84-1.88 (m, 6H), 2.86-2.92 (m, 6H), 3.52-3.62 (m, 2H), 4.06 (s, 6H), 6.16 (brs, 1H), 6.98 (brs, 1H), 7.14 (dd, J=2.7, 9.0 Hz, 1H), 7.30 (d, J=2.7 Hz, 1H), 7.32 (s, 1H), 7.52 (s, 1H), 8.23 (d, J=9.0 Hz, 1H), 8.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 486 (M⁺+1)

Example 678 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-nitrophenyl}-N′-(2-piperidinoethyl)urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (131 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-piperidino-1-ethanamine (56 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (58 mg, yield 40%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.69-1.82 (m, 6H), 2.59-2.81 (m, 6H), 3.49-3.50 (m, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 5.95 (brs, 1H), 6.48 (d, J=5.4 Hz, 1H), 7.44 (s, 1H), 7.47 (d, J=2.9 Hz, 1H), 7.50 (s, 1H), 8.01 (d, J=2.9 Hz, 1H), 8.53 (d, J=5.1 Hz, 1H), 8.73 (d, J=9.3 Hz, 1H), 9.78 (s, 1H)

Example 679 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-nitrophenyl}-N′-(2-piperidinoethyl)urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (131 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-piperidino-1-ethanamine (56 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (79 mg, yield 55%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.49-1.66 (m, 6H), 2.48 (brs, 4H), 2.57 (t, J=5.9 Hz, 2H), 3.43-3.45 (m, 2H), 4.077 (s, 3H), 4.082 (s, 3H), 5.82 (s, 1H), 7.34 (s, 1H), 7.52 (s, 1H) 7.54 (dd, J=2.9, 9.5 Hz, 1H), 8.14 (d, J=2.7 Hz, 1H), 8.61 (s, 1H), 8.81 (d, J=9.5 Hz, 1H), 9.81 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 680 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-methoxyphenyl}-N′-(2-piperidinoethyl)urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-piperidino-1-ethanamine (60 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 54%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.96 (brs, 6H), 2.97-3.02 (m, 6H), 3.59-3.65 (m, 2H), 3.87 (s, 3H), 4.07 (s, 6H), 6.37 (brs, 1H), 6.77 (d, J=2.4 Hz, 1H), 6.81 (dd, J=2.4, 8.8 Hz, 1H), 7.32 (s, 1H), 7.37 (s, 1H), 7.55 (s, 1H), 8.18 (d, J=8.8 Hz, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 482 (M⁺+1)

Example 681 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyphenyl}-N′-(2-piperidinoethyl) urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 2-piperidino-1-ethanamine (60 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (100 mg, yield 67%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 1.97-1.98 (m, 6H), 3.00-3.09 (m, 6H), 3.60-3.68 (m, 2H), 3.85 (s, 3H), 4.050 (s, 3H), 4.054 (s, 3H), 6.42 (brs, 1H), 6.48 (d, J=5.4 Hz, 1H), 6.70 (d, J=2.4 Hz, 1H), 6.76 (dd, J=2.4, 8.8 Hz, 1H), 7.42 (s, 1H), 7.48 (s, 1H), 7.57 (s, 1H), 8.14 (d, J=8.8 Hz, 1H), 8.47 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 682 N-[2-(Dibutylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (151 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-dibutyl-1,2-ethanediamine (88 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (72 mg, yield 43%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.96 (t, J=7.6 Hz, 6H), 1.34-1.42 (m, 4H), 1.65-1.73 (m, 4H), 2.90-2.94 (m, 4H), 3.08 (brs, 2H), 3.59-3.60 (m, 2H), 4.04 (s, 6H), 6.44 (d, J=5.4 Hz, 1H), 7.10 (d, J=9.0 Hz, 2H), 7.41 (s, 1H), 7.52 (d, J=9.0 Hz, 2H), 7.56 (s, 1H), 8.46 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 495 (M⁺+1)

Example 683 N-[2-(Dibutylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-dibutyl-1,2-ethanediamine (81 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (82 mg, yield 51%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.89 (t, J=7.3 Hz, 6H), 1.21-1.28 (m, 4H), 1.35-1.41 (m, 4H), 2.14 (s, 3H), 2.27 (s, 3H), 2.46 (t, J=7.6 Hz, 4H), 2.61-2.64 (m, 2H), 3.34-3.38 (m, 2H), 4.055 (s, 3H), 4.058 (s, 3H), 6.29 (d, J=5.1 Hz, 1H), 6.97 (s, 1H), 7.40 (s, 1H), 7.43 (s, 1H), 7.59 (s, 1H), 8.45 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 684 N-[2-(Dibutylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-dibutyl-1,2-ethanediamine (81 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (80 mg, yield 49%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.86-0.93 (m, 6H), 1.12-1.47 (m, 8H), 2.13 (s, 3H), 2.29 (s, 3H), 2.40-2.49 (m, 4H), 2.57-2.62 (m, 2H), 3.24-3.36 (m, 2H), 4.055 (s, 3H), 4.063 (s, 3H), 6.26 (d, J=5.1 Hz, 1H), 6.98 (d, J=8.5 Hz, 1H), 7.30 (d, J=8.5 Hz, 1H), 7.43 (s, 1H), 7.61 (s, 1H), 8.43 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 685 N-[2-(Dibutylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (151 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-dibutyl-1,2-ethanediamine (88 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (110 mg, yield 65%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.92 (t, J=7.3 Hz, 6H), 1.25-1.32 (m, 4H), 1.45-1.52 (m, 4H), 2.54-2.58 (m, 4H), 2.68-2.71 (m, 2H), 3.36-3.37 (m, 2H), 4.06 (s, 6H), 7.18 (d, J=8.5 Hz, 2H), 7.32 (s, 1H), 7.47 (d, J=8.5 Hz, 2H), 7.55 (s, 1H), 8.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 686 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N′-[2-(dibutylamino)ethyl]urea

2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (134 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-dibutyl-1,2-ethanediamine (78 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (69 mg, yield 43%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.93 (t, J=7.3 Hz, 6H), 1.28-1.33 (m, 4H), 1.40-1.46 (m, 4H), 2.47 (t, J=7.6 Hz, 4H), 2.60-2.63 (m, 2H), 3.32-3.35 (m, 2H), 4.07 (s, 6H), 7.17 (dd, J=2.7, 9.0 Hz, 1H), 7.32 (d, J=2.7 Hz, 1H), 7.33 (s, 1H), 7.52 (s, 1H), 8.19 (d, J=9.0 Hz, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 530 (M⁺+1)

Example 687 N-[2-(Dibutylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (131 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-dibutyl-1,2-ethanediamine (76 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (66 mg, yield 42%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.89-0.96 (m, 6H), 1.27-1.38 (m, 4H), 1.42-1.49 (m, 4H), 2.48 (t, J=7.3 Hz, 4H), 2.62-2.65 (m, 2H), 3.35-3.37 (m, 2H), 4.076 (s, 3H), 4.080 (s, 3H), 7.34 (s, 1H), 7.52-7.56 (m, 2H), 8.14 (d, J=2.9 Hz, 1H), 8.61 (s, 1H), 8.81 (d, J=9.3 Hz, 1H), 9.81 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 541 (M⁺+1)

Example 688 N-[2-(Dibutylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-methoxyphenyl}urea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-methoxyaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-dibutyl-1,2-ethanediamine (81 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (79 mg, yield 49%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.90-0.95 (m, 6H), 1.29-1.36 (m, 4H), 1.44-1.51 (m, 4H), 2.53 (t, J=7.6 Hz, 4H), 2.66-2.69 (m, 2H), 3.35-3.38 (m, 2H), 3.86 (s, 3H), 4.07 (s, 3H), 4.09 (s, 3H), 6.78 (d, J=2.4 Hz, 1H), 6.83 (dd, J=2.4, 8.8 Hz, 1H), 6.96 (brs, 1H), 7.32 (s, 1H), 7.55 (s, 1H), 8.10 (d, J=8.8 Hz, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 526 (M⁺+1)

Example 689 N-[2-(Dibutylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methoxyphenyl}urea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyaniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (139 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, N1,N1-dibutyl-1,2-ethanediamine (81 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (56 mg, yield 34%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 0.90-0.95 (m, 6H), 1.28-1.37 (m, 4H), 1.46-1.54 (m, 4H), 2.56-2.60 (m, 4H), 2.72-2.74 (m, 2H), 3.35-3.43 (m, 2H), 3.84 (s, 3H), 4.05 (s, 6H), 6.48 (d, J=5.1 Hz, 1H), 6.71 (d, J=2.4 Hz, 1H), 6.78 (dd, J=2.4, 8.8 Hz, 1H), 7.42 (s, 1H), 7.57 (s, 1H), 8.09 (d, J=8.5 Hz, 1H), 8.48 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 690 N1-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-4-benzyl-1-piperazinecarboxamide

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (151 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 1-benzylpiperazine (90 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (93 mg, yield 55%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.51 (t, J=4.9 Hz, 4H), 3.52 (t, J=5.1 Hz, 4H), 3.56 (s, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 6.44 (s, 1H), 7.18 (d, J=8.8 Hz, 2H), 7.26-7.35 (m, 5H), 7.47 (d, J=9.0 Hz, 2H), 7.55 (s, 1H), 8.61 (s, 1H)

Example 691 N1-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-4-phenyl-1-piperazinecarboxamide

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (151 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 1-phenylpiperazine (83 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (130 mg, yield 79%)

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.27 (t, J=5.1 Hz, 4H), 3.69 (t, J=5.1 Hz, 4H), 4.066 (s, 3H), 4.072 (s, 3H), 6.50 (s, 1H), 6.90-6.97 (m, 3H), 7.20 (d, J=8.8 Hz, 2H), 7.28-7.32 (m, 2H), 7.49 (d, J=8.8 Hz, 2H), 7.56 (s, 1H), 8.62 (s, 1H)

Example 692 N-[(5-Bromo-2-thienyl)carbonyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methylphenyl}thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 5-bromo-2-thiophenecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 5-bromo-2-thiophene isothiocyanate was prepared using the resultant 5-bromo-2-thiophenecarbonyl chloride as a starting compound according to the description of the literature. 5-Bromo-2-thiophenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 18 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (58 mg, yield 65%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.26 (s, 3H), 3.94 (s, 3H), 3.96 (s, 3H), 6.53 (d, J=5.4 Hz, 1H), 7.11-7.16 (m, 1H), 7.21-7.24 (m, 1H), 7.37-7.45 (m, 2H), 7.49-7.54 (m, 1H), 7.82-7.85 (m, 1H), 8.51 (d, J=5.1 Hz, 1H), 10.04 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 559 (M⁺+1)

Example 693 N-[(5-Bromo-2-thienyl)carbonyl]-N′-[3-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 5-bromo-2-thiophenecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 5-bromo-2-thiophene isothiocyanate was prepared using the resultant 5-bromo-2-thiophenecarbonyl chloride as a starting compound according to the description of the literature. 5-Bromo-2-thiophenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 18 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (65 mg, yield 75%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.39 (d, J=5.4 Hz, 1H), 7.39-7.43 (m, 2H), 7.45-7.55 (m, 2H), 7.77-7.81 (m, 1H), 7.88 (d, J=4.1 Hz, 1H), 8.12 (d, J=2.4 Hz, 1H), 8.49 (d, J=5.1 Hz, 1H), 10.55 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 579 (M⁺+1)

Example 694 N-[(5-Chloro-2-thienyl)carbonyl]-N′-{4[(6,7-dimethoxy-4-quinolyl)oxy]-2-methylphenyl}thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 5-chloro-2-thiophenecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 5-chloro-2-thiophene isothiocyanate was prepared using the resultant 5-chloro-2-thiophenecarbonyl chloride as a starting compound according to the description of the literature. 5-Chloro-2-thiophenecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (43 mg, yield 52%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.26 (s, 3H), 3.93 (s, 3H), 3.95 (s, 3H), 6.52 (d, J=5.1 Hz, 1H), 7.11-7.15 (m, 1H), 7.21-7.23 (m, 1H), 7.27-7.29 (m, 1H), 7.38-7.46 (m, 3H), 7.86-7.88 (m, 1H), 8.51 (d, J=5.1 Hz, 1H), 10.05-10.08 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 514 (M⁺+1)

Example 695 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[(5-chloro-2-thienyl)carbonyl]-thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 5-chloro-2-thiophenecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 5-chloro-2-thiophene isothiocyanate was prepared using the resultant 5-chloro-2-thiophenecarbonyl chloride as a starting compound according to the description of the literature. 5-Chloro-2-thiophenecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (46 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.38 (d, J=5.4 Hz, 1H), 7.31 (d, J=4.1 Hz, 1H), 7.41 (s, 1H), 7.46 (s, 1H), 7.49 (s, 1H), 7.77-7.82 (m, 1H), 7.92-7.95 (m, 1H), 8.10-8.12 (m, 1H), 8.48 (d, J=5.1 Hz, 1H), 10.57 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 535 (M⁺+1)

Example 696 N-{4-[(6,7-Dimethoxy-4-quinolyl)-oxy]-2-methylphenyl}-N′-[3-(methylthio)propanoyl]-thiourea

3-(Methylthio)propanoyl isothiocyanate was prepared using commercially available 3-(methylthio)propanoyl chloride (80 mg) as a starting compound according to the description of the literature. 3-(Methylthio)propanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 19 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (27 mg, yield 35%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.10 (s, 3H), 2.24 (s, 3H), 2.74-2.84 (m, 4H), 3.93 (s, 3H), 3.95 (s, 3H), 6.55 (d, J=5.4 Hz, 1H), 7.11-7.72 (m, 5H), 8.52 (d, J=5.4 Hz, 1H), 11.57-11.60 (bs, 1H), 12.10-12.13 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 472 (M⁺+1)

Example 697 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[3-(methylthio)propanoyl]thiourea

3-(Methylthio)propanoyl isothiocyanate was prepared using commercially available 3-(methylthio)propanoyl chloride (80 mg) as a starting compound according to the description of the literature. 3-(Methylthio)propanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (14 mg, yield 18%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.10 (s, 3H), 2.71-2.84 (m, 4H), 3.94 (s, 3H), 3.96 (s, 3H), 6.41 (d, J=5.4 Hz, 1H), 7.31-7.72 (m, 5H), 8.50 (d, J=5.1 Hz, 1H), 11.63-11.66 (bs, 1H), 12.49-12.52 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 698 N-{4-[(6,7-Dimethoxy-4-quinolyl)-oxy]-2-methylphenyl}-N′-[(2,5-dimethyl-3-furyl)-carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,5-dimethyl-3-furoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,5-dimethyl-3-furancarbonyl isothiocyanate was prepared using the resultant 2,5-dimethyl-3-furancarbonyl chloride as a starting compound according to the description of the literature. 2,5-Dimethyl-3-furancarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 15 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (41 mg, yield 52%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.26 (s, 3H), 2.28 (s, 3H), 2.55 (s, 3H), 3.93 (s, 3H), 3.96 (s, 3H), 6.56 (d, J=5.1 Hz, 1H), 6.90 (s, 1H), 7.14 (dd, J=2.7, 8.8 Hz, 1H), 7.23 (d, J=2.7 Hz, 1H), 7.41 (s, 1H), 7.50 (s, 1H), 7.67 (t, J=8.7 Hz, 1H), 8.53 (d, J=5.1 Hz, 1H), 10.97-11.00 (bs, 1H), 12.33-12.36 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 699 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[(2,5-dimethyl-3-furyl)-carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,5-dimethyl-3-furoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,5-dimethyl-3-furancarbonyl isothiocyanate was prepared using the resultant 2,5-dimethyl-3-furancarbonyl chloride as a starting compound according to the description of the literature. 2,5-Dimethyl-3-furancarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 15 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (38 mg, yield 50%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.26 (s, 3H), 2.55 (s, 3H), 3.95 (s, 3H), 3.96 (s, 3H), 6.42 (d, J=5.1 Hz, 1H), 6.89 (s, 1H), 7.43 (s, 1H), 7.49 (d, J=8.8 Hz, 1H), 7.53 (s, 1H), 7.70-7.76 (m, 1H), 8.16-8.21 (m, 1H), 8.51 (d, J=5.1 Hz, 1H), 11.03-11.05 (bs, 1H), 12.71-12.74 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 512 (M⁺+1)

Example 700 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylphenyl}-N′-[2-(2-thienyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-thienyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-thienyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-thienyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Thienyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 15 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (18 mg, yield 23%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.23 (s, 3H), 3.81 (s, 1H), 3.95 (s, 3H), 3.98 (s, 3H), 4.08 (s, 1H), 6.63 (d, J=5.4 Hz, 1H), 6.93-7.05 (m, 3H), 7.16-7.19 (m, 1H), 7.24-7.27 (m, 1H), 7.36-7.46 (m, 3H), 7.55 (s, 1H), 7.70 (d, J=8.8 Hz, 1H), 8.60 (d, J=5.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 701 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(2-thienyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-thienyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-thienyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-thienyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Thienyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (15 mg, yield 20%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.81 (s, 1H), 4.00 (s, 3H), 4.02 (s, 3H), 4.08 (s, 1H), 6.68 (d, J=5.6 Hz, 1H), 6.93-7.05 (m, 3H), 7.37-7.40 (m, 1H), 7.44-7.47 (m, 1H), 7.49 (s, 1H), 7.58 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 7.74-7.79 (m, 1H), 8.16-8.20 (m, 1H), 8.71 (d, J=5.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 514 (M⁺+1)

Example 702 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(2-methylphenyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-methylphenyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-methylphenyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-methylphenyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Methylphenyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]-aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (45 mg, yield 57%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.30 (s, 3H), 3.89 (s, 2H), 3.96 (s, 3H), 3.98 (s, 3H), 6.51 (d, J=5.6 Hz, 1H), 7.12-7.28 (m, 5H), 7.45 (s, 1H), 7.50 (d, J=9.0 Hz, 1H), 7.58 (s, 1H), 7.70-7.75 (m, 1H), 8.58 (d, J=5.6 Hz, 1H), 11.80-11.83 (bs, 1H), 12.44-12.48 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 522 (M⁺+1)

Example 703 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[2-(2-methylphenyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-methylphenyl)acetic acid (80 mg), and the mixture was heated 100° C. for one hr. The solvent was removed by distillation, and 2-(2-methylphenyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-methylphenyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Methylphenyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (36 mg, yield 43%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.30 (s, 3H), 3.88 (s, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 7.14-7.36 (m, 7H), 7.39 (s, 1H), 7.56 (s, 1H), 7.70-7.75 (m, 1H), 8.55-8.57 (bs, 1H), 11.70-11.73 (bs, 1H), 12.39-12.42 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 489 (M⁺+1)

Example 704 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-cyclohexylacetyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-cyclohexylacetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-cyclohexylethanoyl isothiocyanate was prepared using the resultant 2-cyclohexylethanoyl chloride as a starting compound according to the description of the literature. 2-Cyclohexylethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]-aniline (50 mg), toluene (5 ml), and ethanol (1 ml)-were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (36 mg, yield 46%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.88-1.30 (m, 5H), 1.58-1.80 (m, 6H), 2.07 (d, J=6.6 Hz, 1H), 2.37 (d, J=7.1 Hz, 1H), 3.94 (s, 3H), 3.96 (s, 3H), 6.41 (d, J=5.4 Hz, 1H), 7.42 (s, 1H), 7.47 (d, J=8.8 Hz, 1H), 7.53 (s, 1H), 7.67-7.72 (m, 1H), 8.14-8.18 (m, 1H), 8.51 (d, J=5.1 Hz, 1H), 11.53-11.56 (bs, 1H), 12.59-12.63 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 514 (M⁺+1)

Example 705 N-(2-Cyclohexylacetyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-cyclohexylacetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-cyclohexylethanoyl isothiocyanate was prepared using the resultant 2-cyclohexylethanoyl chloride as a starting compound according to the description of the literature. 2-Cyclohexylethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (30 mg, yield 44%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.93-1.30 (m, 5H), 1.58-1.81 (m, 6H), 2.37 (d, J=7.1 Hz, 2H), 3.98 (s, 3H), 3.99 (s, 3H), 7.35 (d, J=8.8 Hz, 2H), 7.40 (s, 1H), 7.57 (s, 1H), 7.73 (d, J=9.0 Hz, 2H), 8.57 (s, 1H), 11.44-11.47 (bs, 1H), 12.58 (d, J=4.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 706 N-Benzyl-N′-{3-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was added to toluene (2 ml) and ethanol (2 ml) to prepare a solution. Benzyl isothiocyanate (48 μl) was then added to the solution, and the mixture was stirred at 80° C. for 6 hr. The reaction solution was concentrated, and ether and hexane were added to the residue. The resultant crystal was collected by filtration to give the title compound (46 mg, yield 65%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 4.77 (d, J=5.1 Hz, 1H), 6.42 (d, J=5.4 Hz, 1H), 7.25-7.55 (m, 9H), 7.95-8.01 (bs, 1H), 8.37-8.43 (bs, 1H), 8.51 (d, J=5.1 Hz, 1H), 9.80-9.86 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 707 N-Benzyl-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

4□[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (4 ml) and ethanol (6 ml) to prepare a solution. Benzyl isothiocyanate (81 μl) was added to the solution, and the mixture was stirred at 80° C. for 6 hr. The reaction solution was concentrated, and ether and hexane were added to the residue. The resultant crystal was collected by filtration to give the title compound (74 mg, yield 98%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.97 (s, 3H), 3.99 (s, 3H), 4.73-4.79 (bs, 2H), 7.24-7.56 (m, 11H), 8.18-8.25 (bs, 1H), 8.55 (s, 1H), 9.63-9.67 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 447 (M⁺+1)

Example 708 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(1-naphthyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(1-naphthyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(1-naphthyl)ethanoyl isothiocyanate was prepared using the resultant 2-(1-naphthyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(1-Naphthyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (67 mg, yield 78%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.94 (s, 3H), 3.96 (s, 3H), 4.36 (s, 2H), 6.45 (d, J=5.4 Hz, 1H), 7.41-8.15 (m, 12H), 8.53 (d, J=5.4 Hz, 1H), 11.97-12.00 (bs, 1H), 12.39-12.42 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 558 (M⁺+1)

Example 709 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[2-(1-naphthyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(1-naphthyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(1-naphthyl)ethanoyl isothiocyanate was prepared using the resultant 2-(1-naphthyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(1-Naphthyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (24 mg, yield 27%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.92 (s, 3H), 3.95 (s, 3H), 4.08 (s, 2H), 6.68 (d, J=8.8 Hz, 1H), 7.29-8.16 (m, 13H), 8.63 (s, 1H), 10.03 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 710 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(2-naphthyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-naphthyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-naphthyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-naphthyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-naphthyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]-aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (25 mg, yield 29%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.74 (s, 2H), 3.98 (s, 3H), 4.00 (s, 3H), 6.62 (d, J=6.4 Hz, 1H), 7.40-7.93 (m, 11H), 8.15-8.20 (m, 1H), 8.66 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 558 (M⁺+1)

Example 711 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[2-(2-naphthyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-naphthyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-naphthyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-naphthyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Naphthyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (33 mg, yield 38%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.74 (s, 2H), 3.91 (s, 3H), 3.92 (s, 3H), 6.68 (d, J=8.8 Hz, 1H), 7.29-7.52 (m, 6H), 7.77-7.90 (m, 6H), 8.31 (s, 1H), 8.64-8.68 (bs, 1H), 9.96 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 712 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[3-(3,4-dimethoxyphenyl)-propanoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-(3,4-dimethoxyphenyl)propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-(3,4-dimethoxyphenyl)propanoyl isothiocyanate was prepared using the resultant 3-(3,4-dimethoxyphenyl)propanoyl chloride as a starting compound according to the description of the literature. 3-(3,4-Dimethoxyphenyl)propanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]-aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (32 mg, yield 36%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.94 (t, J=7.3 Hz, 2H), 2.72-2.89 (m, 2H), 3.69-3.76 (m, 6H), 3.99 (d, J=5.6 Hz, 3H), 6.57 (d, J=5.6 Hz, 1H), 6.70-6.89 (m, 3H), 7.47 (s, 1H), 7.54 (d, J=8.8 Hz, 1H), 7.62 (s, 1H), 7.70-7.76 (m, 1H), 8.16-8.20 (m, 1H), 8.63 (d, J=5.6 Hz, 1H), 11.63-11.64 (bs, 1H), 12.55-12.58 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 582 (M⁺+1)

Example 713 N-[3-(3,4-Dimethoxyphenyl)propanoyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-(3,4-dimethoxyphenyl)propanoic acid (80 mg), and the mixtue was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-(3,4-dimethoxyphenyl)propanoyl isothiocyanate was prepared using the resultant 3-(3,4-dimethoxyphenyl)propanoyl chloride as a starting compound according to the description of the literature. 3-(3,4-Dimethoxyphenyl)propanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (37 mg, yield 40%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.94 (t, J=7.3 Hz, 2H), 2.59-2.65 (m, 1H), 2.84-2.89 (m, 1H), 3.71 (s, 3H), 3.73 (s, 3H), 3.98 (d, J=5.9 Hz, 3H), 6.68-6.88 (m, 4H), 7.23 (d, J=8.5 Hz, 2H), 7.38 (s, 1H), 7.55 (s, 1H), 7.67 (d, J=8.8 Hz, 2H), 8.53 (s, 1H), 10.00 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 549 (M⁺+1)

Example 714 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(2-chlorophenoxy)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-chlorophenoxy)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-chlorophenoxy)ethanoyl isothiocyanate was prepared using the resultant 2-(2-chlorophenoxy)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Chlorophenoxy)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (29 mg, yield 37%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.95 (s, 3H), 4.88 (s, 2H), 6.35 (d, J=5.1 Hz, 1H), 6.95-7.13 (m, 3H), 7.26-7.67 (m, 6H), 8.05-8.07 (bs, 1H), 8.30-8.32 (bs, 1H), 8.47 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 715 N-[2-(2-Chlorophenoxy)acetyl]-N′-{4-(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-chlorophenoxy)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-chlorophenoxy)ethanoyl isothiocyanate was prepared using the resultant 2-(2-chlorophenoxy)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Chlorophenoxy)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (21 mg, yield 21%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 4.55 (s, 6H), 4.76 (s, 2H), 6.71 (d, J=8.5 Hz, 1H), 6.95-7.47 (m, 10H), 9.24 (s, 1H), 9.84 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 716 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(4-ethoxybenzoyl)thiourea

4-Ethoxy-1-benzenecarbonyl isothiocyanate was prepared using 4-ethoxy-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-Ethoxy-1-benzenecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (72 mg, yield 89%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.37 (t, J=7.1 Hz, 3H), 3.99 (s, 3H), 4.00 (s, 3H), 4.15 (q, J=7.1 Hz, 2H), 7.06 (d, J=8.8 Hz, 2H), 7.35-7.41 (m, 3H), 7.58 (s, 1H), 7.75-7.82 (m, 2H), 8.03 (d, J=8.8 Hz, 2H), 8.58 (s, 1H), 11.40 (d, J=2.9 Hz, 1H), 12.74-12.75 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 505 (M⁺+1)

Example 717 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N′-[(2,5-dimethyl-3-furyl)carbonyl]-thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,5-dimethyl-3-furoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,5-dimethyl-3-furancarbonyl isothiocyanate was prepared using the resultant 2,5-dimethyl-3-furancarbonyl chloride as a starting compound according to the description of the literature. 2,5-Dimethyl-3-furancarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethyl-aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (69 mg, yield 96%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.11 (s, 3H), 2.23 (s, 3H), 2.26 (s, 3H), 2.55 (s, 3H), 3.95 (s, 6H), 6.35 (d, J=5.4 Hz, 1H), 6.91 (s, 1H), 7.16 (s, 1H), 7.41 (s, 1H), 7.55-7.61 (m, 2H), 8.49 (d, J=5.1 Hz, 1H), 10.98-11.10 (bs, 1H), 11.31-11.34 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 718 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[(2,5-dimethyl-3-furyl)carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,5-dimethyl-3-furoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,5-dimethyl-3-furancarbonyl isothiocyanate was prepared using the resultant 2,5-dimethyl-3-furancarbonyl chloride as a starting compound according to the description of the literature. 2,5-Dimethyl-3-furancarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (77 mg, yield 95%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.26 (s, 3H), 2.55 (s, 3H), 3.98 (s, 3H), 4.00 (s, 3H), 6.89 (s, 1H), 7.34-7.41 (m, 3H), 7.58 (s, 1H), 7.73-7.81 (m, 2H), 8.58 (s, 1H), 10.93 (d, J=3.9 Hz, 1H), 12.67-12.70 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 479 (M⁺+1)

Example 719 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-pentanoylthiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available pentanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and pentanoyl isothiocyanate was prepared using the resultant pentanoyl chloride as a starting compound according to the description of the literature. Pentanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (29 mg, yield 41%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.90 (t, J=7.6 Hz, 3H), 1.28-1.39 (m, 2H), 1.52-1.63 (m, 2H), 3.95 (s, 3H), 3.97 (s, 3H), 6.45 (d, J=5.1 Hz, 1H), 7.43 (s, 1H), 7.49 (d, J=8.8 Hz, 1H), 7.55 (s, 1H), 7.67-7.73 (m, 1H), 8.14-8.18 (m, 1H), 8.53 (d, J=5.4 Hz, 1H), 11.57 (d, J=2.7 Hz, 1H), 12.58 (d, J=4.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 720 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-pentanoylthiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available pentanoic acid (80 mg) at 100° C. for one hr. The solvent was removed by distillation, and pentanoyl isothiocyanate was prepared using the resultant pentanoyl chloride as a starting compound according to the description of the literature. Pentanoyl isothiocyanate thus obtanined was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (17 mg, yield 23%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.86 (t, J=7.3 Hz, 3H), 1.23-1.40 (m, 2H), 1.50-1.64 (m, 2H), 3.12-3.19 (m, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 7.21-7.25 (m, 2H), 7.38 (s, 1H), 7.55 (s, 1H), 7.66-7.70 (m, 2H), 8.53 (s, 1H), 9.97 (s, 1H).

Mass spectrometry value (ESI-MS, m/z): 441 (M⁺+1)

Example 721 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[3-(4-methylphenyl)propanoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-(4-methylphenyl)propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-(4-methylphenyl)propanoyl isothiocyanate was prepared using the resultant 3-(4-methylphenyl)propanoyl chloride as a starting compound according to the description of the literature. 3-(4-Methylphenyl)propanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (90 mg, yield 99%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.25 (s, 3H), 2.47 (s, 2H), 2.76 (t, J=7.6 Hz, 2H), 3.93 (s, 3H), 3.95 (s, 3H), 6.54 (d, J=5.1 Hz, 1H), 7.04-7.16 (m, 4H), 7.30 (d, J=8.8 Hz, 2H), 7.41 (s, 1H), 7.50 (s, 1H), 7.73-7.79 (m, 2H), 8.51 (d, J=5.1 Hz, 1H), 11.51-11.54 (bs, 1H), 12.04-12.10 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 722 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[3-(4-methylphenyl)propanoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-(4-methylphenyl)propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-(4-methylphenyl)propanoyl isothiocyanate was prepared using the resultant 3-(4-methylphenyl)propanoyl chloride as a starting compound according to the description of the literature. 3-(4-Methylphenyl)propanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (54 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.25 (s, 3H), 2.47 (s, 2H), −2.62 (t, J=7.3 Hz, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 6.67 (d, J=9.0 Hz, 1H), 7.04-7.39 (m, 7H), 7.55 (s, 3H), 7.64-7.68 (m, 2H), 8.53 (s, 1H), 10.00 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 503 (M⁺+1)

Example 723 N-[2-(2-Chlorophenyl)acetyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-chlorophenyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-chlorophenyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-chlorophenyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Chlorophenyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (77 mg, yield 89%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.92 (s, 3H), 3.95 (s, 3H), 4.04 (s, 2H), 6.54 (d, J=5.1 Hz, 1H), 7.27-7.50 (m, 7H), 7.74-7.79 (m, 2H), 8.31 (s, 1H), 8.51 (d, J=5.1 Hz, 1H), 11.80-11.83 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 724 N-[2-(2-Chlorophenyl)acetyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-chlorophenyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-chlorophenyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-chlorophenyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Chlorophenyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (43 mg, yield 49%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.86 (s, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 7.22-7.48 (m, 8H), 7.56 (s, 1H), 7.66-7.71 (m, 2H), 8.53 (s, 1H), 10.33 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 509 (M⁺+1)

Example 725 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(4-phenylbutanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-phenylbutanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-phenylbutanoyl isothiocyanate was prepared using the resultant 4-phenylbutanoyl chloride as a starting compound according to the description of the literature. 4-Phenylbutanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (50 mg, yield 59%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.07-1.12 (m, 4H), 2.72-2.88 (m, 2H), 3.93 (s, 3H), 3.96 (s, 3H), 6.55 (d, J=5.4 Hz, 1H), 7.19-7.35 (m, 7H), 7.41 (s, 1H), 7.51 (s, 1H), 7.72-7.78 (m, 2H), 8.52 (d, J=5.1 Hz, 1H), 11.50-11.53 (bs, 1H), 12.48 (d, J=4.9 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 726 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(4-phenylbutanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-phenylbutanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-phenylbutanoyl isothiocyanate was prepared using the resultant 4-phenylbutanoyl chloride as a starting compound according to the description of the literature. 4-Phenylbutanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (56 mg, yield 70%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.23-1.28 (m, 4H), 2.72-2.88 (m, 2H), 3.94 (s, 3H), 3.96 (s, 3H), 6.42 (d, J=5.4 Hz, 1H), 7.18-7.35 (m, 5H), 7.43 (s, 1H), 7.47 (d, J=8.8 Hz, 1H), 7.53 (s, 1H), 7.64-7.70 (m, 1H), 8.11-8.15 (m, 1H), 8.51 (d, J=8.4 Hz, 1H), 11.58-11.61 (bs, 1H), 12.50 (d, J=4.9 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 536 (M⁺+1)

Example 727 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(5-phenylpentanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 5-phenylpentanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-phenylpentanoyl isothiocyanate was prepared using the resultant 4-phenylpentanoyl chloride as a starting compound according to the description of the literature. 4-Phenylpentanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (41 mg, yield 47%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.56-1.64 (m, 4H) 2.57-2.63 (m, 2H), 3.94 (s, 3H), 3.96 (s, 3H), 6.58 (d, J=5.4 Hz, 1H), 7.15-7.34 (m, 7H), 7.42 (s, 1H), 7.53 (s, 1H), 7.75-7.81 (m, 2H), 8.55 (d, J=5.4 Hz, 1H), 11.48 (d, J=2.9 Hz, 1H), 12.53 (d, J=4.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 516 (M⁺+1)

Example 728 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-phenylpentanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 5-phenylpentanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-phenylpentanoyl isothiocyanate was prepared using the resultant 4-phenylpentanoyl chloride as a starting compound according to the description of the literature. 4-Phenylpentanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (47 mg, yield 57%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.56-1.64 (m, 4H), 2.56-2.63 (m, 2H), 3.95 (s, 3H), 3.9.6 (s, 3H), 6.44 (d, J=5.4 Hz, 1H), 7.15-7.32 (m, 5H), 7.43 (s, 1H), 7.48 (d, J=8.8 Hz, 1H), 7.54 (s, 1H), 7.67-7.72 (m, 1H), 8.13-8.18 (m, 1H), 8.53 (d, J=5.4 Hz, 1H), 11.55-11.59 (bs, 1H), 12.55 (d, J=4.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 550 (M⁺+1)

Example 729 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[2-(2-fluorophenyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-fluorophenyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-fluorophenyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-fluorophenyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Fluorophenyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (55 mg, yield 66%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.76 (s, 2H), 3.93 (s, 3H), 3.95 (s, 3H), 6.46 (d, J=5.4 Hz, 1H), 7.10-7.52 (m, 8H), 7.71-7.76 (m, 2H), 8.31 (s, 1H), 8.47 (d, J=5.1 Hz, 1H), 10.36 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 730 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(2-fluorophenyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-fluorophenyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-fluorophenyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-fluorophenyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Fluorophenyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (51 mg, yield 65%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.78 (s, 2H), 3.96 (s, 3H), 3.97 (s, 3H), 6.44 (d, J=5.6 Hz, 1H), 7.10-7.64 (m, 8H), 8.06 (d, J=2.2 Hz, 1H), 8.31 (s, 1H), 8.53 (d, J=5.6 Hz, 1H), 10.56 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 526 (M⁺+1)

Example 731 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[3-(2-methylphenyl)propanoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-(2-methylphenyl)propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-(2-methylphenyl)propanoyl isothiocyanate was prepared using the resultant 3-(2-methylphenyl)propanoyl chloride as a starting compound according to the description of the literature. 3-(2-Methylphenyl)propanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (14 mg, yield 16%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.31 (s, 3H), 2.73-2.93 (m, 4H), 3.94 (s, 3H), 3.96 (s, 3H), 6.57 (d, J=5.1 Hz, 1H), 7.08-7.19 (m, 4H), 7.32 (d, J=8.8 Hz, 2H), 7.42 (s, 1H), 7.52 (s, 1H), 7.74-7.81 (m, 2H), 8.53 (d, J=5.4 Hz, 1H), 11.54-11.57 (bs, 1H), 12.53 (d, J=2.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 732 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[3-(2-methylphenyl)propanoyl]-thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-(2-methylphenyl)propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-(2-methylphenyl)propanoyl isothiocyanate was prepared using the resultant 3-(2-methylphenyl)propanoyl chloride as a starting compound according to the description of the literature. 3-(2-Methylphenyl)propanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (45 mg, yield 56%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.31 (s, 3H), 2.74-2.92 (m, 4H), 3.97 (s, 3H), 3.98 (s, 3H), 6.51 (d, J=5.6 Hz, 1H), 7.08-7.20 (m, 4H), 7.45 (s, 1H), 7.52 (d, J=8.8 Hz, 1H), 7.58 (s, 1H), 7.69-7.75 (m, 1H), 8.15-8.19 (m, 1H), 8.58 (d, J=5.4 Hz, 1H), 11.65 (d, J=2.4 Hz, 1H), 12.56 (d, J=4.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 536 (M⁺+1)

Example 733 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[2-(2-methoxyphenyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-methoxyphenyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-methoxyphenyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-methoxyphenyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Methoxyphenyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (25 mg, yield 30%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.79 (s, 3H), 3.82 (s, 2H), 3.96 (s, 3H), 3.99 (s, 3H), 6.66 (d, J=5.9 Hz, 1H), 6.85-7.03 (m, 2H), 7.21-7.37 (m, 4H), 7.44 (s, 1H), 7.58 (s, 1H), 7.78-7.84 (m, 2H), 8.62 (d, J=5.9 Hz, 1H), 11.64-11.66 (bs, 1H), 12.47 (d, J=4.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 504 (M⁺+1)

Example 734 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(2-methoxyphenyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-methoxyphenyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-methoxyphenyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-methoxyphenyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Methoxyphenyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (45 mg, yield 55%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.79 (s, 3H), 3.82 (s, 2H), 3.99 (s, 3H), 4.01 (s, 3H), 6.66 (d, J=5.9 Hz, 1H), 6.85-7.03 (m, 2H), 7.22-7.32 (m, 2H), 7.49 (s, 1H), 7.56 (d, J=9.0 Hz, 1H), 7.66 (s, 1H), 7.74-7.80 (m, 1H), 8.20-8.24 (m, 1H), 8.69 (d, J=5.9 Hz, 1H), 11.75 (d, J=2.4 Hz, 1H), 12.52 (d, J=4.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 538 (M⁺+1)

Example 735 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[2-(2-nitrophenyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-nitrophenyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-nitrophenyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-nitrophenyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Nitrophenyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/methanol for development to give the title compound (7 mg, yield 8%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 4.00 (s, 3H), 4.00 (s, 3H), 4.30 (s, 2H), 6.71 (d, J=5.9 Hz, 1H), 7.33-7.84 (m, 8H), 8.08 (d, J=7.8 Hz, 1H), 8.67 (d, J=5.9 Hz, 1H), 11.84-11.88 (bs, 1H), 12.25-12.28 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 519 (M⁺+1)

Example 736 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(2-nitrophenyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-nitrophenyl)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-nitrophenyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-nitrophenyl)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Nitrophenyl)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/methanol for development to give the title compound (8 mg, yield 10%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.94 (s, 3H), 3.96 (s, 3H), 4.30 (s, 2H), 6.41 (d, J=5.1 Hz, 1H), 7.40-7.80 (m, 7H), 8.10-8.17 (m, 2H), 8.50 (d, J=5.1 Hz, 1H), 11.91-11.94 (bs, 1H), 12.26 (d, J=4.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 553 (M⁺+1)

Example 737 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-phenoxyacetyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-phenoxyacetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-phenoxyethanoyl isothiocyanate was prepared using the resultant 2-phenoxyethanoyl chloride as a starting compound according to the description of the literature. 2-Phenoxyethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (40 mg, yield 48%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.94 (s, 3H), 3.96 (s, 3H), 4.73 (s, 2H), 6.49 (d, J=5.1 Hz, 1H), 6.88-7.05 (m, 3H), 7.24-7.36 (m, 4H), 7.40 (s, 1H), 7.53 (s, 1H), 7.80 (d, J=9.0 Hz, 2H), 8.50 (d, J=5.4 Hz, 1H), 10.25 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 490 (M⁺+1)

Example 738 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-phenoxyacetyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-phenoxyacetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-phenoxyethanoyl isothiocyanate was prepared using the resultant 2-phenoxyethanoyl chloride as a starting compound according to the description of the literature. 2-Phenoxyethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (50 mg, yield 64%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.99 (s, 3H), 4.00 (s, 3H), 4.76 (s, 2H), 6.57 (d, J=5.6 Hz, 1H), 6.88-7.05 (m, 3H), 7.26-7.37 (m, 3H), 7.46 (s, 1H), 7.51 (d, J=9.0 Hz, 1H), 7.63 (s, 1H), 7.73-7.78 (m, 1H), 8.12 (d, J=2.2 Hz, 1H), 8.61 (d, J=5.9 Hz, 1H), 10.44 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 524 (M⁺+1)

Example 739 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[2-(2-methylphenoxy)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-methylphenoxy)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-methylphenoxy)ethanoyl isothiocyanate was prepared using the resultant 2-(2-methylphenoxy)ethanoyl chloride as a starting compound according to the description of the literature. 2-(2-Methylphenoxy)ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (25 mg, yield 29%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.27 (s, 3H), 3.94 (s, 3H), 3.95 (s, 3H), 4.74 (s, 2H), 6.46 (d, J=5.1 Hz, 1H), 6.78-6.92 (m, 3H), 7.09-7.28 (m, 4H), 7.40 (s, 1H), 7.51 (s, 1H), 7.78 (d, J=8.8 Hz, 2H), 8.47 (d, J=5.1 Hz, 1H), 10.20 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 504 (M⁺+1)

Example 740 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(2-methylphenoxy)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-methylphenoxy)acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-methylphenoxy)ethanoyl isothiocyanate was prepared using the resultant 2-(2-methylphenoxy)ethanoyl chloride as a starting compound according to the description of the literature. 2-Phenoxyethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (26 mg, yield 32%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.27 (s, 3H), 3.96 (s, 3H), 3.96 (s, 3H), 4.77 (s, 2H), 6.42 (d, J=5.4 Hz, 1H), 6.78-7.71 (m, 9H), 8.09 (d, J=2.4 Hz, 1H), 8.51 (d, J=5.4 Hz, 1H), 10.39 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 538 (M⁺+1)

Example 741 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-phenoxybutanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-phenoxybutanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-phenoxybutanoyl isothiocyanate was prepared using the resultant 2-phenoxybutanoyl chloride as a starting compound according to the description of the literature. 2-Phenoxybutanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (35 mg, yield 40%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.05 (t, J=7.3 Hz, 3H), 1.87-2.01 (m, 2H), 3.92 (s, 3H), 3.95 (s, 3H), 4.95-5.00 (m, 1H), 6.54 (d, J=5.4 Hz, 1H), 6.88-7.02 (m, 3H), 7.25-7.37 (m, 4H), 7.41 (s, 1H), 7.49 (s, 1H), 7.73-7.80 (m, 2H), 8.52 (d, J=5.4 Hz, 1H), 11.73-11.76 (bs, 1H), 12.16 (d, J=4.9 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 518 (M⁺+1)

Example 742 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-phenoxybutanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-phenoxybutanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-phenoxybutanoyl isothiocyanate was prepared using the resultant 2-phenoxybutanoyl chloride as a starting compound according to the description of the literature. 2-Phenoxybutanoyl isothiocyanate thus obatined was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (25 mg, yield 27%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.06 (t, J=7.6 Hz, 3H), 1.86-2.02 (m, 2H), 3.94 (s, 3H), 3.96 (s, 3H), 4.95-5.01 (m, 1H), 6.40 (d, J=5.4 Hz, 1H), 6.90-7.02 (m, 3H), 7.30-7.37 (m, 2H), 7.42 (s, 1H), 7.46 (d, J=8.8 Hz, 1H), 7.52 (s, 1H), 7.67-7.73 (m, 1H), 8.10-8.15 (m, 1H), 8.51 (d, J=5.4 Hz, 1H), 11.82-11.86 (bs, 1H), 12.17 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 552 (M⁺+1)

Example 743 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[(2R)-2-phenylpropanoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available (2R)-2-phenylpropanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and (2R)-2-phenylpropanoyl isothiocyanate was prepared using the resultant (2R)-2-phenylpropanoyl chloride as a starting compound according to the description of the literature. (2R)-2-Phenylpropanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (31 mg, yield 38%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.44 (d, J=7.1 Hz, 3H), 3.92 (s, 3H), 3.95 (s, 3H), 4.08-4.16 (m, 1H), 6.55 (d, J=5.4 Hz, 1H), 7.24-7.45 (m, 8H), 7.50 (s, 1H), 7.72-7.78 (m, 2H), 8.52 (d, J=5.1 Hz, 1H), 11.66-11.69 (bs, 1H), 12.41-12.44 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 744 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[(2R)-2-phenylpropanoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available (2R)-2-phenylpropanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and (2R)-2-phenylpropanoyl isothiocyanate was prepared using the resultant (2R)-2-phenylpropanoyl chloride as a starting compound according to the description of the literature. (2R)-2-Phenylpropanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (56 mg, yield 71%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.44 (d, J=6.8 Hz, 3H), 3.94 (s, 3H), 3.96 (s, 3H), 4.08-4.16 (m, 1H), 6.42 (d, J=5.4 Hz, 1H), 7.27%-7.49 (m, 7H), 7.53 (s, 1H), 7.66-7.72 (m, 1H), 8.10-8.14 (m, 1H), 8.52 (d, J=5.1 Hz, 1H), 11.75-11.78 (bs, 1H), 12.44-12.47 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 522 (M⁺+1)

Example 745 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-phenoxypropanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-phenoxypropanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-phenoxypropanoyl isothiocyanate was prepared using the resultant 2-phenoxypropanoyl chloride as a starting compound according to the description of the literature. 2-Phenoxypropanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (14 mg, yield 16%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.58 (d, J=6.6 Hz, 3H), 3.93 (s, 3H), 3.95 (s, 3H), 4.86-4.93 (m, 1H), 6.44 (d, J=5.1 Hz, 1H), 6.96-7.01 (m, 3H), 7.21-7.35 (m, 4H), 7.39 (s, 1H), 7.50 (s, 1H), 7.75-7.80 (m, 2H), 8.46 (d, J=5.4 Hz, 1H), 10.27 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 504 (M⁺+1)

Example 746 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-phenoxypropanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-phenoxypropanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-phenoxypropanoyl isothiocyanate was prepared using the resultant 2-phenoxypropanoyl chloride as a starting compound according to the description of the literature. 2-Phenoxypropanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (33 mg, yield 41%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.58 (d, J=6.6 Hz, 3H), 3.94 (s, 3H), 3.95 (s, 3H), 4.87-4.94 (m, 1H), 6.35 (d, J=5.1 Hz, 1H), 6.88-7.53 (m, 8H), 7.69-7.74 (m, 1H), 8.07 (d, J=2.4 Hz, 1H), 8.45 (d, J=5.4 Hz, 1H), 10.43 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 538 (M⁺+1)

Example 747 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-phenylbutanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-phenylbutanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-phenylbutanoyl isothiocyanate was prepared using the resultant 2-phenylbutanoyl chloride as a starting compound according to the description of the literature. 2-Phenylbutanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (41 mg, yield 48%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.86 (t, J=7.3 Hz, 3H), 1.22-1.28 (bs, 1H), 1.69-1.81 (m, 1H), 2.01-2.14 (m, 1H), 3.93 (s, 3H), 3.95 (s, 3H), 6.55 (d, J=5.4 Hz, 1H), 7.26-7.44 (m, 8H), 7.50 (s, 1H), 7.72-7.79 (m, 2H), 8.53 (d, J=5.1 Hz, 1H), 11.69-11.72 (bs, 1H), 12.44-12.48 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 748 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-phenylbutanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-phenylbutanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-phenylbutanoyl isothiocyanate was prepared using the resultant 2-phenylbutanoyl chloride as a starting compound according to the description of the literature. 2-Phenylbutanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (37 mg, yield 46%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.83-0.90 (m, 3H), 1.22-1.29 (bs, 1H), 1.69-1.81 (m, 1H), 2.01-2.14 (m, 1H), 3.94 (s, 3H), 3.95 (s, 3H), 6.40 (d, J=5.1 Hz, 1H), 7.28-7.47 (m, 7H), 7.52 (s, 1H), 7.66-7.72 (m, 1H), 8.10-8.14 (m, 1H), 8.50 (d, J=5.1 Hz, 1H), 11.77-11.80 (bs, 1H), 12.45-12.48 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 536 (M⁺+1)

Example 749 N-[(2,2-Dichloro-1-methylcyclopropyl)-carbonyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,2-dichloro-1-methyl-1-cyclopropanecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,2-dichloro-1-methyl-1-cyclopropanecarbonyl isothiocyanate was prepared using the resultant 2,2-dichloro-1-methyl-1-cyclopropanecarbonyl chloride as a starting compound according to the description of the literature. 2,2-Dichloro-1-methyl-1-cyclopropanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (63 mg, yield 73%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.67 (s, 3H), 1.71 (d, J=8.1 Hz, 1H), 2.13 (d, J=7.8 Hz, 1H), 3.93 (s, 3H), 3.95 (s, 3H), 6.55 (d, J=5.1 Hz, 1H), 7.28-7.34 (m, 2H), 7.41 (s, 1H), 7.50 (s, 1H), 7.75-7.81 (bs, 2H), 8.52 (d, J=5.1 Hz, 1H), 12.11-12.20 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 750 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[(2,2-dichloro-1-methylcyclopropyl)carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,2-dichloro-1-methyl-1-cyclopropanecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,2-dichloro-1-methyl-1-cyclopropanecarbonyl isothiocyanate was prepared using the resultant 2,2-dichloro-1-methyl-1-cyclopropanecarbonyl chloride as a starting compound according to the description of the literature. 2,2-Dichloro-1-methyl-1-cyclopropanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (27 mg, yield 34%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.67 (s, 3H), 1.72 (d, J=7.8 Hz, 1H), 2.13 (d, J=7.8 Hz, 1H), 3.95 (s, 3H), 3.96 (s, 3H), 6.42 (d, J=4.4 Hz, 1H), 7.43 (s, 1H), 7.48 (d, J=8.8 Hz, 1H), 7.53 (s, 1H), 7.67-7.74 (bs, 1H), 8.13-8.18 (bs, 1H), 8.51 (d, J=5.1 Hz, 1H), 12.19-12.23 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 540 (M⁺+1)

Example 751 N-(4-Butoxybenzoyl)-N′-[4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-butoxybenzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-butoxy-1-benzenecarbonyl isothiocyanate was prepared using the resultant 4-butoxy-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-Butoxy-1-benzenecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (59 mg, yield 65%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.95 (t, J=7.6 Hz, 3H), 1.40-1.52 (m, 2H), 1.69-1.78 (m, 2H), 3.94 (s, 3H), 3.96 (s, 3H), 4.06-4.12 (m, 2H), 6.56 (d, J=5.1 Hz, 1H), 7.05-7.11 (m, 2H), 7.30-7.36 (m, 2H), 7.42 (s, 1H), 7.51 (s, 1H), 7.80-7.87 (m, 2H), 8.00-8.05 (m, 2H), 8.52 (d, J=5.1 Hz, 1H), 11.40-11.43 (bs, 1H), 12.72-12.76 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 532 (M⁺+1)

Example 752 N-(4-Butoxybenzoyl)-N′-{3-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-butoxybenzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-butoxy-1-benzenecarbonyl isothiocyanate was prepared using the resultant 4-butoxy-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-Butoxy-1-benzenecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (55 mg, yield 65%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.92-0.99 (m, 3H), 1.40-1.52 (m, 2H), 1.69-1.79 (m, 2H), 3.95 (s, 3H), 3.96 (s, 3H), 4.06-4.12 (m, 2H), 6.43 (d, J=5.1 Hz, 1H), 7.05-7.11 (m, 2H), 7.42-7.56 (m, 3H), 7.73-7.79 (m, 1H), 8.00-8.06 (m, 2H), 8.18-8.24 (m, 1H), 8.52 (d, J=5.4 Hz, 1H), 11.50-11.54 (bs, 1H), 12.74-12.79 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 566 (M⁺+1)

Example 753 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[4-(pentyloxy)benzoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-(pentyloxy)benzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-(pentyloxy)-1-benzenecarbonyl isothiocyanate was prepared using the resultant 4-(pentyloxy)-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-(Pentyloxy)-1-benzenecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (61 mg, yield 65%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.88-0.94 (m, 3H), 1.31-1.46 (m, 4H), 1.71-1.80 (m, 2H), 3.94 (s, 3H), 3.96 (s, 3H), 4.08 (t, J=6.3 Hz, 2H), 6.56 (d, J=5.1 Hz, 1H), 7.04-7.10 (m, 2H), 7.30-7.36 (m, 2H), 7.42 (s, 1H), 7.51 (s, 1H), 7.80-7.87 (m, 2H), 8.00-8.05 (m, 2H), 8.52 (d, J=5.4 Hz, 1H), 11.40-11.43 (bs, 1H), 12.73-12.76 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 546 (M⁺+1)

Example 754 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[4-(pentyloxy)benzoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-(pentyloxy)benzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-(pentyloxy)-1-benzenecarbonyl isothiocyanate was prepared using the resultant 4-(pentyloxy)-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-(Pentyloxy)-1-benzenecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (63 mg, yield 72%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.88-0.94 (m, 3H), 1.31-1.47 (m, 4H), 1.71-1.80 (m, 2H), 3.95 (s, 3H), 3.96 (s, 3H), 4.08 (t, J=6.6 Hz, 2H), 6.43 (d, J=5.1 Hz, 1H), 7.05-7.10 (m, 2H), 7.43 (s, 1H), 7.50 (d, J=8.8 Hz, 1H), 7.54 (s, 1H), 7.72-7.79 (m, 1H), 8.00-8.05 (m, 2H), 8.18-8.24 (m, 1H), 8.51 (d, J=5.1 Hz, 1H), 11.49-11.53 (bs, 1H), 12.74-12.78 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 580 (M⁺+1)

Example 755 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[4-(hexyloxy)benzoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-(hexyloxy)benzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-(hexyloxy)-1-benzenecarbonyl isothiocyanate was prepared using the resultant 4-(hexyloxy)-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-(Hexyloxy)-1-benzenecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (58 mg, yield 61%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.86-0.92 (m, 3H), 1.29-1.35 (m, 4H), 1.39-1.48 (m, 2H), 1.70-1.79 (m, 2H), 3.94 (s, 3H), 3.96 (s, 3H), 4.05-4.11 (m, 2H), 6.56 (d, J=5.1 Hz, 1H), 7.04-7.10 (m, 2H), 7.30-7.36 (m, 2H), 7.42 (s, 1H), 7.51 (s, 1H), 7.80-7.87 (m, 2H), 8.00-8.05 (m, 2H), 8.52 (d, J=5.4 Hz, 1H), 11.39-11.43 (bs, 1H), 12.72-12.76 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 560 (M⁺+1)

Example 756 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[4-(hexyloxy)benzoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-(hexyloxy)benzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-(hexyloxy)-1-benzenecarbonyl isothiocyanate was prepared using the resultant 4-(hexyloxy)-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-(Hexyloxy)-1-benzenecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (56 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.86-0.91 (m, 3H), 1.28-1.35 (m, 4H), 1.39-1.47 (m, 2H), 1.70-1.79 (m, 2H), 3.95 (s, 3H), 3.96 (s, 3H), 4.08 (t, J=6.3 Hz, 2H), 6.43 (d, J=5.1 Hz, 1H), 7.05-7.10 (m, 2H), 7.43 (s, 1H), 7.50 (d, J=9.0 Hz, 1H), 7.54 (s, 1H), 7.72-7.78 (m, 1H), 8.00-8.05 (m, 2H), 8.18-8.25 (m, 1H), 8.51 (d, J=5.1 Hz, 1H), 11.49-11.52 (bs, 1H), 12.73-12.77 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 595 (M⁺+1)

Example 757 N-[2-(4-Chlorophenoxy)-2-methylpropanoyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(4-chlorophenoxy)-2-methylpropanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(4-chlorophenoxy)-2-methylpropanoyl isothiocyanate was prepared using the resultant 2-(4-chlorophenoxy)-2-methylpropanoyl chloride as a starting compound according to the description of the literature. 2-(4-Chlorophenoxy)-2-methylpropanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (39 mg, yield 41%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.56 (s, 6H), 3.93 (s, 3H), 3.96 (s, 3H), 6.56 (d, J=5.1 Hz, 1H), 7.07-7.13 (m, 2H), 7.31-7.53 (m, 6H), 7.78-7.85 (m, 2H), 8.53 (d, J=5.1 Hz, 1H), 10.54-10.57 (bs, 1H), 12.10-12.15 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 552 (M⁺+1)

Example 758 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(4-chlorophenoxy)-2-methylpropanoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(4-chlorophenoxy)-2-methylpropanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(4-chlorophenoxy)-2-methylpropanoyl isothiocyanate was prepared using the resultant 2-(4-chlorophenoxy)-2-methylpropanoyl chloride as a starting compound according to the description of the literature. 2-(4-Chlorophenoxy)-2-methylpropanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (17 mg, yield 19%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.56 (s, 6H), 3.95 (s, 3H), 3.96 (s, 3H), 6.42 (d, J=5.1 Hz, 1H), 7.07-7.12 (m, 2H), 7.38-7.55 (m, 5H), 7.71-7.78 (m, 1H), 8.13-8.19 (m, 1H), 8.52 (d, J=5.1 Hz, 1H), 10.67-10.71 (bs, 1H), 12.13-12.17 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 587 (M⁺+1)

Example 759 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2,2,3,3-tetramethylcyclopropyl)carbonyl]-thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,2,3,3-tetramethylcyclopropanecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,2,3,3-tetramethyl-1-cyclopropanecarbonyl isothiocyanate was prepared using the resultant 2,2,3,3-tetramethyl-1-cyclopropanecarbonyl chloride as a starting compound according to the description of the literature. 2,2,3,3-Tetramethyl-1-cyclopropanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (11 mg, yield 14%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.20 (s, 6H), 1.27 (s, 6H), 1.73 (s, 1H), 3.93 (s, 3H), 3.95 (s, 3H), 6.54 (d, J=5.4 Hz, 1H), 7.26-7.32 (m, 2H), 7.41 (s, 1H), 7.50 (s, 1H), 7.73-7.80 (m, 2H), 8.51 (d, J=5.1 Hz, 1H), 11.41-11.45 (bs, 1H), 12.55-12.59 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 760 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,2,3,3-tetramethylcyclopropanecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,2,3,3-tetramethyl-1-cyclopropanecarbonyl isothiocyanate was prepared using the resultant 2,2,3,3-tetramethyl-1-cyclopropanecarbonyl chloride as a starting compound according to the description of the literature. 2,2,3,3-Tetramethyl-1-cyclopropanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (17 mg, yield 21%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.21 (s, 6H), 1.27 (s, 6H), 1.71-1.75 (m, 1H), 3.95 (s, 3H), 3.96 (s, 3H), 6.41 (d, J=5.1 Hz, 1H), 7.43 (s, 1H), 7.46 (d, J=8.5 Hz, 1H), 7.53 (s, 1H), 7.66-7.72 (m, 1H), 8.12-8.18 (m, 1H), 8.51 (d, J=5.1 Hz, 1H), 11.50-11.53 (bs, 1H), 12.59 (d, J=4.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 514 (M⁺+1)

Example 761 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-methoxy-2-phenylacetyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-methoxy-2-phenylacetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-methoxy-2-phenylethanoyl isothiocyanate was prepared using the resultant 2-methoxy-2-phenylethanoyl chloride as a starting compound according to the description of the literature. 2-Methoxy-2-phenylethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (25 mg, yield 30%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.40 (s, 3H), 3.93 (s, 3H), 3.94 (s, 3H), 4.54 (s, 1H), 4.87 (s, 1H), 6.43 (d, J=5.1 Hz, 1H), 7.20-7.54 (m, 9H), 7.80-7.86 (m, 2H), 8.45 (d, J=5.1 Hz, 1H), 10.20 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 503 (M⁺+1)

Example 762 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-methoxy-2-phenylacetyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-methoxy-2-phenylacetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-methoxy-2-phenylethanoyl isothiocyanate was prepared using the resultant 2-methoxy-2-phenylethanoyl chloride as a starting compound according to the description of the literature. 2-Methoxy-2-phenylethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (28 mg, yield 35%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.40 (s, 3H), 3.94 (s, 3H), 3.95 (s, 3H), 4.54 (s, 1H), 4.88 (s, 1H), 6.33 (d, J=5.1 Hz, 1H), 7.28-7.55 (m, 8H), 7.77-7.83 (m, 1H), 8.11-8.16 (m, 1H), 8.44 (d, J=5.1 Hz, 1H), 10.37 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 537 (M⁺+1)

Example 763 N-[2-(2-Chlorophenoxy)propanoyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-chlorophenoxy)propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-chlorophenoxy)propanoyl isothiocyanate was prepared using the resultant 2-(2-chlorophenoxy)propanoyl chloride as a starting compound according to the description of the literature. 2-(2-Chlorophenoxy)propanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (4 mg, yield 5%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.62 (d, J=6.6 Hz, 3H), 3.93 (s, 3H), 3.95 (s, 3H), 4.96 (q, J=6.6 Hz, 1H), 6.46 (d, J=5.1 Hz, 1H), 6.98-7.52 (m, 8H), 7.74-7.79 (m, 2H), 8.47 (d, J=5.1 Hz, 1H), 10.31 (s, 1H).

Mass spectrometry value (ESI-MS, m/z): 537 (M⁺+1)

Example 764 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(2-chlorophenoxy)propanoyl]-thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-chlorophenoxy)propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-chlorophenoxy)propanoyl isothiocyanate was prepared using the resultant 2-(2-chlorophenoxy)propanoyl chloride as a starting compound according to the description of the literature. 2-(2-Chlorophenoxy)propanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (53 mg, yield 62%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.62 (d, J=6.8 Hz, 3H), 3.95 (s, 3H), 3.95 (s, 3H), 4.93-5.01 (m, 1H), 6.37 (d, J=5.4 Hz, 1H), 6.95-7.55 (m, 8H), 7.67-7.71 (m, 1H), 8.07 (s, 1H), 8.47 (d, J=5.4 Hz, 1H), 10.50 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 572 (M⁺+1)

Example 765 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-tetrahydro-2-furanylcarbonylthiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available tetrahydro-2-furancarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and tetrahydro-2-furancarbonyl isothiocyanate was prepared using the resultant tetrahydro-2-furancarbonyl chloride as a starting compound according to the description of the literature. Tetrahydro-2-furancarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (5 mg, yield 6%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.84-1.92 (m, 2H), 1.97-2.06 (m, 1H), 2.17-2.27 (m, 1H), 3.82-3.88 (m, 1H), 3.94 (s, 3H), 3.95 (s, 3H), 3.97-4.04 (m, 1H), 4.39-4.44 (m, 1H), 6.45 (d, J=5.1 Hz, 1H), 7.21-7.26 (m, 2H), 7.40 (s, 1H), 7.52 (s, 1H), 7.84 (d, J=9.0 Hz, 2H), 8.48 (d, J=5.4 Hz, 1H), 9.83 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 454 (M⁺+1)

Example 766 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-tetrahydro-2-furanylcarbonylthiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available tetrahydro-2-furancarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and tetrahydro-2-furancarbonyl isothiocyanate was prepared using the resultant tetrahydro-2-furancarbonyl chloride as a starting compound according to the description of the literature. Tetrahydro-2-furancarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (5 mg, yield 7%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.84-1.92 (m, 2H), 1.97-2.06 (m, 1H), 2.17-2.27 (m, 1H), 3.83-3.89 (m, 1H), 3.95 (s, 3H), 3.96 (s, 3H), 3.97-4.03 (m, 1H), 4.41-4.46 (m, 1H), 6.38 (d, J=5.4 Hz, 1H), 7.42 (s, 1H), 7.44 (s, 1H), 7.55 (s, 1H), 7.79-7.84 (m, 1H), 8.15 (d, J=2.4 Hz, 1H), 8.49 (d, J=5.4 Hz, 1H), 10.01 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 767 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[(3-methoxycyclohexyl)carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-methoxy-1-cyclohexanecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-methoxy-1-cyclohexanecarbonyl isothiocyanate was prepared using the resultant 3-methoxy-1-cyclohexanecarbonyl chloride as a starting compound according to the description of the literature. 3-Methoxy-1-cyclohexanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (38 mg, yield 45%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.32-1.61 (m, 5H), 1.73-1.85 (m, 2H), 1.90-1.97 (m, 1H), 2.85-2.94 (m, 1H), 3.25 (s, 3H), 3.53-3.58 (bs, 1H), 3.93 (s, 3H), 3.96 (s, 3H), 6.56 (d, J=5.1 Hz, 1H), 7.30 (d, J=8.8 Hz, 2H), 7.41 (s, 1H), 7.51 (s, 1H), 7.74-7.80 (m, 2H), 8.53 (d, J=5.4 Hz, 1H), 11.48-11.51 (bs, 1H), 12.57 (d, J=4.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 768 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[(3-methoxycyclohexyl)carbonyl]-thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-methoxy-1-cyclohexanecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-methoxy-1-cyclohexanecarbonyl isothiocyanate was prepared using the resultant 3-methoxy-1-cyclohexanecarbonyl chloride as a starting compound according to the description of the literature. 3-Methoxy-1-cyclohexanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (31 mg, yield 39%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.33-1.61 (m, 5H), 1.73-1.85 (m, 2H), 1.90-1.97 (m, 1H), 2.85-2.94 (m, 1H), 3.25 (s, 3H), 3.53-3.57 (bs, 1H), 3.95 (s, 3H), 3.96 (s, 3H), 6.43 (d, J=5.1 Hz, 1H), 7.43 (s, 1H), 7.48 (d, J=8.8 Hz, 1H), 7.54 (s, 1H), 7.67-7.72 (m, 1H), 8.14-8.18 (m, 1H), 8.53 (d, J=5.4 Hz, 1H), 11.59 (d, J=2.9 Hz, 1H), 12.59 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 530 (M⁺+1)

Example 769 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-ethoxyacetyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-ethoxyacetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-ethoxyethanoyl isothiocyanate was prepared using the resultant 2-ethoxyethanoyl chloride as a starting compound according to the description of the literature. 2-Ethoxyethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (9 mg, yield 13%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.21 (t, J=7.1 Hz, 3H), 3.55-3.62 (m, 2H), 3.96 (s, 3H), 3.97 (s, 3H), 4.06 (s, 2H), 6.54 (d, J=5.4 Hz, 1H), 7.26 (d, J=8.8 Hz, 2H), 7.42 (s, 1H), 7.56 (s, 1H), 7.82 (d, J=9.0 Hz, 2H), 8.54 (d, J=5.6 Hz, 1H), 9.87 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): (M⁺+1)

Example 770 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-{[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy}acetyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-{[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy}acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-{([(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy}ethanoyl isothiocyanate was prepared using the resultant 2-{[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy}ethanoyl chloride as a starting compound according to the description of the literature. 2-{[(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl]oxy}ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (27 mg, yield 29%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.77 (d, J=6.8 Hz, 3H), 0.81-1.00 (m, 9H), 1.23-1.40 (m, 1H), 1.56-1.67 (m, 2H), 2.09-2.15 (m, 1H), 2.24-2.34 (m, 1H), 3.94 (s, 3H), 3.95 (s, 3H), 4.02-4.16 (m, 2H), 6.47 (d, J=5.4 Hz, 1H), 7.22-7.27 (m, 2H), 7.40 (s, 1H), 7.52 (s, 1H), 7.76-7.81 (m, 2H), 8.48 (d, J=5.4 Hz, 1H), 9.72 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 551 (M⁺+1)

Example 771 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-{[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy}acetyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-{[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy}acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-{[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy}ethanoyl isothiocyanate was prepared using the resultant 2-{[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]oxy}ethanoyl chloride as a starting compound according to the description of the literature. 2-{[(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl]oxy}ethanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (17 mg, yield 19%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.77 (d, J=6.8 Hz, 3H), 0.80-1.02 (m, 9H), 1.23-1.40 (m, 1H), 1.56-1.67 (m, 2H), 2.08-2.14 (m, 1H), 2.23-2.34 (m, 1H), 3.95 (s, 3H), 3.96 (s, 3H), 4.04-4.18 (m, 2H), 6.36 (d, J=5.1 Hz, 1H), 7.41 (s, 1H), 7.43 (d, J=8.8 Hz, 1H), 7.54 (s, 1H), 7.70-7.74 (m, 1H), 8.09 (d, J=2.4 Hz, 1H), 8.48 (d, J=5.1 Hz, 1H), 9.93 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 585 (M⁺+1)

Example 772 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-phenyl benzoate

Chlorobenzene (7 ml) was added to 4-chloro-6,7-dimethoxyquinazoline (2.5 g) and 4-hydroxyphenyl benzoate (4.78 g), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. Methanol was added to the residue, and the precipitated crystal was collected by filtration and was washed to give the title compound (3.49 g, yield 78%).

¹H-NMR (chloroform-d, 400 MHz): δ 4.10 (s, 3H), 4.10 (s, 3H), 7.31-7.38 (m, 4H), 7.49 (s, 1H), 7.51-7.59 (m, 3H), 7.64-7.69 (m, 1H), 8.20-8.25 (m, 2H), 8.68 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 403 (M⁺+1)

Example 773 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-phenol

Methanol (5 ml) and sodium hydroxide (0.2 g) were added to 4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl benzoate (500 mg), and the mixture was stirred at 0° C. for 30 min. A saturated aqueous ammonium chloride solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. Methanol was added to the residue, and the precipitated crystal was collected by filtration and was washed to give the title compound (350 mg, yield 95%).

¹H-NMR (chloroform-d, 400 MHz): δ 4.08 (s, 3H), 4.11 (s, 3H), 6.91-6.95 (m, 2H), 7.05-7.10 (m, 2H), 7.57 (s, 1H), 7.59 (s, 1H), 8.66 (s, 1H)

Mass spectrometry value (FD-MS, m/z): 298 (M⁺)

Example 774 Methyl 2-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenoxy}acetate

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenol (100 mg) was dissolved in dimethylformamide (2 ml) to prepare a solution. Sodium hydride (15 mg) was added to the solution, and the mixture was stirred at 0° C. for 10 min. Methylbromoacetate (0.037 ml) was added thereto, and the mixture was further stirred at 0° C. for 30 min. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. Diethyl ether was added to the residue, and the precipitated crystal was collected by filtration and was washed to give the title compound (88 mg, yield 71%).

¹H-NMR (chloroform-d, 400 MHz): δ 3.84 (s, 3H), 4.07 (s, 6H), 4.67 (s, 2H), 6.99-7.04 (m, 2H), 7.17-7.21 (m, 2H), 7.33 (s, 1H), 7.55 (s, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 371 (M⁺+1)

Example 775 2-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenoxy}acetic acid

Methyl 2-{4-[(6,7-dimethoxy-4-quinazolinyloxy)-phenol (70 mg) was dissolved in methanol (1 ml) to prepare a solution. A solution of sodium hydroxide (70 mg) in water was added to the solution, and the mixture was stirred at 0° C. for 2 hr. Concentrated hydrochloric acid was added to the reaction solution, and the precipitated crystal was collected by filtration and was washed with methanol, diethyl ether, and hexane to give the title compound (65 mg, yield 97%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.98 (s, 3H), 3.99 (s, 3H), 4.73 (s, 2H), 6.97-7.02 (m, 2H), 7.20-7.25 (m, 2H), 7.39 (s, 1H), 7.56 (s, 1H), 8.56 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 357 (M⁺+1)

Example 776 N1-(2-Methoxyphenyl)-2-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenoxy}acetamide

2-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenoxy}acetic acid (150 mg), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (WSC.HCl) (122 mg), and 1-hydroxybenzotriazole hydrate (HOBT.H₂O) (86 mg) were dissolved in chloroform (5 ml) to prepare a solution. o-Anisidine (63 mg) was then added to the solution, and the mixture was heated under reflux for 3 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was washed with 1 N hydrochloric acid, water, and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (155 mg, yield 80%).

The compound (50 mg) thus obtained was dissolved in 10% hydrochloric acid-methanol solution (6 ml), and the solution was allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 49 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.88 (s, 3H), 4.04 (s, 3H), 4.05 (s, 3H), 4.77 (s, 1H), 4.86 (s, 1H), 6.80-6.83 (m, 1H), 6.93-6.97 (m, 1H), 7.09-7.42 (m, 6H), 7.64 (s, 1H), 7.75 (d, J=2.7 Hz, 1H), 8.05-8.09 (m, 1H), 8.79-8.82 (m, 1H), 9.29 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 461 (M⁺+1)

Example 777 N-(2-{4-[(6,7-Dimethoxy-4-quinolyl)-oxy]phenoxy}ethyl)-N-(2-methoxyphenyl)amine

N1-(2-Methoxyphenyl)-2-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenoxy}acetamide (100 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A borane-tetrahydrofuran complex (1.0 M solution: 1.08 ml) was then added to the solution, and the mixture was heated under reflux for 5 hr. 1 N Hydrochloric acid was added thereto, and the mixture was further heated under reflux for 30 min. A 5% aqueous sodium hydroxide solution was added to the reaction solution, the mixture was extracted with chloroform, and the extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (58 mg, yield 60%).

The resultant compound (55 mg) was dissolved in 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 20 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 55 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.53 (t, J=5.4 Hz, 2H), 3.80 (s, 3H), 4.04 (s, 3H), 4.05 (s, 3H), 4.23 (t, J=5.6 Hz, 2H), 6.66-6.72 (m, 1H), 6.75-6.91 (m, 4H), 7.18 (d, J=9.0 Hz, 2H), 7.36 (d, J=9.0 Hz, 2H), 7.63 (s, 1H), 7.76 (s, 1H), 8.80 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 447 (M⁺+1)

Example 778 N1-(3-Methoxyphenyl)-2-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenoxy}acetamide

2-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenoxy}acetic acid (150 mg), WSC.HCl (122 mg), and HOBT.H₂O (86 mg) were dissolved in chloroform (5 ml) to prepare a solution. m-Anisidine (63 mg) was then added to the solution, and the mixture was heated under reflux for 3 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was washed with 1 N hydrochloric acid, water, and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (173 mg, yield 89%).

The resultant compound (45 mg) was dissolved in 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 42 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.74 (s, 3H), 4.04 (s, 3H), 4.05 (s, 3H), 4.77 (s, 1H), 4.80 (s, 1H), 6.67-6.70 (m, 1H), 6.80-6.83 (m, 1H), 7.13-7.40 (m, 7H), 7.62 (s, 1H), 7.75 (s, 1H), 8.80 (d, J=6.8 Hz, 1H), 10.20 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 461 (M⁺+1)

Example 779 N-(2-{4-[(6,7-Dimethoxy-4-quinolyl)-oxy]phenoxy}ethyl)-N-(3-methoxyphenyl)amine

N1-(3-Methoxyphenyl)-2-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenoxy}acetamide (112 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A borane-tetrahydrofuran complex (1.0 M solution: 1.22 ml) was then added to the solution, and the mixture was heated under reflux for 5 hr. 1 N Hydrochloric acid was added thereto, and the mixture was further heated under reflux for 30 min. A 5% aqueous sodium hydroxide solution was added to the reaction solution, the mixture was extracted with chloroform, and the extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (64 mg, yield 59%).

The resultant compound (60 mg) was dissolved in a 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 20 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 58 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.59 (t, J=5.1 Hz, 2H), 3.73 (s, 3H), 4.04 (s, 6H), 4.26 (t, J=5.1 Hz, 2H), 6.53-6.70 (m, 3H), 6.80 (d, J=6.8 Hz, 1H), 7.15-7.22 (m, 3H), 7.35-7.40 (m, 2H), 7.76 (d, J=5.1 Hz, 2H), 8.81 (d, J=6.8 Hz, 1H)

Mass spectrometry value (ESI MS, m/z): 447 (M⁺+1)

Example 780 N1-(4-Methoxyphenyl)-2-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenoxy}acetamide

2-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenoxy}acetic acid (150 mg), WSC.HCl (122 mg), and HOBT.H₂O (86 mg) were dissolved in chloroform (5 ml) to prepare a solution. p-Anisidine (63 mg) was then added to the solution, and the mixture was heated under reflux for 4 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was washed with 1 N hydrochloric acid, water, and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (147 mg, yield 76%).

The resultant compound (47 mg) was dissolved in a 10% hydrochloric acid-methanol solution (6 ml) which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 49 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.73 (s, 3H), 4.03 (s, 3H), 4.04 (s, 3H), 4.76 (s, 2H), 6.80 (d, J=6.8 Hz, 1H), 6.90-6.92 (m, 2H), 7.12-7.40 (m, 4H), 7.55-7.63 (m, 3H), 7.74 (s, 1H), 8.79 (d, J=6.6 Hz, 1H), 10.05 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 461 (M⁺+1)

Example 781 N-(2-{4-[(6,7-Dimethoxy-4-quinolyl)-oxy]phenoxy}ethyl)-N-(4-methoxyphenyl)amine

N1-(4-Methoxyphenyl)-2-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenoxy}acetamide (90 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A borane-tetrahydrofuran complex (1.0 M solution: 0.98 ml) was then added to the solution, and the mixture was heated under reflux for 3 hr. 1 N Hydrochloric acid was added thereto, and the mixture was further heated under reflux for 30 min. A 5% aqueous sodium hydroxide solution was added to the reaction solution, the mixture was extracted with chloroform, and the extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (52 mg, yield 60%).

The resultant compound (52 mg) was dissolved in a 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 20 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 42 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.54-3.62 (m, 2H), 3.70-3.74 (m, 3H), 4.04 (s, 3H), 4.04 (s, 3H), 4.21-4.26 (m, 2H), 6.81 (d, J=6.6 Hz, 1H), 6.87-6.97 (m, 2H), 7.12-7.21 (m, 2H), 7.35-7.39 (m, 2H), 7.57-7.63 (m, 2H), 7.75 (s, 2H), 8.80 (d, J=6.8 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 447 (M⁺+1)

Example 782 N1-(2-Methylphenyl)-2-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenoxy}acetamide

2-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenoxy}acetic acid (150 mg), WSC.HCl (122 mg), and HOBT.H₂O (86 mg) were dissolved in chloroform (5 ml) to prepare a solution. o-Toluidine (0.055 ml) was then added to the solution, and the mixture was heated under reflux for 6 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (103 mg, yield 55%).

The resultant compound (101 mg) was dissolved in a 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 100 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.20 (s, 3H), 4.04 (s, 3H), 4.05 (s, 3H), 4.77 (s, 1H), 4.83 (s, 1H), 6.79-6.83 (m, 1H), 7.11-7.46 (m, 8H), 7.63-7.69 (m, 1H), 7.76 (s, 1H), 7.76 (s, 1H), 8.82 (d, J=6.6 Hz, 1H), 9.60 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 783 N-(2-{4-[(6,7-Dimethoxy-4-quinolyl)-oxy]phenoxy}ethyl)-N-(2-methylphenyl)amine

N1-(2-Methylphenyl)-2-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenoxy}acetamide (65 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A borane-tetrahydrofuran complex (1.0 M solution: 0.74 ml) was then added to the solution, and the mixture was heated under reflux overnight. 1 N Hydrochloric acid was added thereto, and the mixture was further heated under reflux for 30 min. A 5% aqueous sodium hydroxide solution was added to the reaction solution, the mixture was extracted with chloroform, and the extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (29 mg, yield 46%).

The resultant compound (29 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 20 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 30 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.16 (s, 3H), 3.57 (t, J=5.9 Hz, 2H), 4.04 (s, 3H), 4.05 (s, 3H), 4.25 (t, J=5.6 Hz, 2H), 6.63-6.70 (m, 1H), 6.77-6.84 (m, 2H), 7.02-7.12 (m, 2H), 7.16-7.21 (m, 2H), 7.34-7.39 (m, 2H), 7.66 (s, 1H), 7.76 (s, 1H), 8.80 (d, J=6.8 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 431 (M⁺+1)

Example 784 N1-(3-Methylphenyl)-2-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenoxy}acetamide

2-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenoxy}acetic acid (150 mg), WSC.HCl (122 mg), and HOBT.H₂O (86 mg) were dissolved in chloroform (5 ml) to prepare a solution. m-Toluidine (0.055 ml) was then added to the solution, and the mixture was heated under reflux for 4 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was washed with 1 N hydrochloric acid, water, and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (102 mg, yield 55%).

The resultant compound (30 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 20 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 27 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.29 (s, 3H), 4.03 (s, 3H), 4.05 (s, 3H), 4.76 (s, 1H), 4.79 (s, 1H), 6.78-6.83 (m, 1H), 6.89-6.93 (m, 1H), 7.01-7.51 (m, 7H), 7.61 (s, 1H), 7.75 (s, 1H), 8.79 (d, J=6.6 Hz, 1H), 10.12 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 785 N-(2-{4-[(6,7-Dimethoxy-4-quinolyl)-oxy]phenoxy}ethyl)-N-(3-methylphenyl)amine

N1-(3-Methylphenyl)-2-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenoxy}acetamide (70 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A borane-tetrahydrofuran complex (1.0 M solution: 0.78 ml) was then added to the solution, and the mixture was heated under reflux overnight. 1 N Hydrochloric acid was added thereto, and the mixture was further heated under reflux for 30 min. A 5% aqueous sodium hydroxide solution was added to the reaction solution, the mixture was extracted with chloroform, and the extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (31 mg, yield 46%).

The resultant compound (31 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 20 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 31 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.23 (s, 3H), 3.49-3.53 (m, 2H), 4.04 (s, 3H), 4.05 (s, 3H), 4.20 (t, J=5.1 Hz, 2H), 6.53-6.60 (m, 1H), 6.60-6.70 (m, 1H), 6.81 (s, 1H), 6.82 (s, 1H), 7.03-7.10 (m, 1H), 7.15-7.20 (m, 2H), 7.34-7.39 (m, 2H), 7.64 (s, 1H), 7.76 (s, 1H), 8.81 (d, J=6.8 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 431 (M⁺+1)

Example 786 N1-(4-Methylphenyl)-2-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenoxy}acetamide

2-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenoxy}acetic acid (150 mg), WSC.HCl (122 mg), and HOBT.H₂O (86 mg) were dissolved in chloroform (5 ml) to prepare a solution. p-Toluidine (0.055 ml) was then added to the solution, and the mixture was heated under reflux for 3 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was washed with 1 N hydrochloric acid, water, and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (76 mg, yield 41%).

The resultant compound (20 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 16 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.27 (s, 3H), 4.03 (s, 3H), 4.04 (s, 3H), 4.76 (s, 1H), 4.78 (s, 1H), 6.78-6.82 (m, 1H), 7.12-7.16 (m, 2H), 7.19-7.25 (m, 2H), 7.36-7.40 (m, 2H), 7.52-7.57 (m, 2H), 7.63 (s, 1H), 7.74 (s, 1H), 8.79 (d, J=6.6 Hz, 1H), 10.13 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 787 N-(2-[4-[(6,7-Dimethoxy-4-quinolyl)-oxy]phenoxy}ethyl)-N-(4-methylphenyl)amine

N1-(4-Methylphenyl)-2-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenoxy}acetamide (54 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A borane-tetrahydrofuran complex (1.0 M solution: 0.60 ml) was then added to the solution, and the mixture was heated under reflux for 3 hr. 1 N Hydrochloric acid was added thereto, and the mixture was further heated under reflux for 30 min. A 5% aqueous sodium hydroxide solution was added to the reaction solution, the mixture was extracted with chloroform, and the extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (11 mg, yield 20%).

The resultant compound (11 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 20 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 11 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.24 (s, 3H), 3.54-3.60 (m, 2H), 4.04 (s, 3H), 4.05 (s, 3H), 4.16-4.27 (m, 2H), 6.81 (d, J=6.6 Hz, 1H), 6.74-7.28 (m, 4H), 7.32-7.42 (m, 2H), 7.68-7.79 (m, 2H), 7.67 (s, 1H), 7.76 (s, 1H), 8.80 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 431 (M⁺+1)

Example 788 N1-(3-Chlorophenyl)-2-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenoxy}acetamide

2-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenoxy}acetic acid (150 mg), WSC.HCl (122 mg), and HOBT.H₂O (86 mg) were dissolved in chloroform (5 ml) to prepare a solution. m-Chloroaniline (65 mg) was then added to the solution, and the mixture was heated under reflux for 3 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was washed with 1 N hydrochloric acid, water, and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (141 mg, yield 72%).

The resultant compound (50 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 40 mg of a hydrochloride.

Mass spectrometry value (ESI-MS, m/z): 465 (M⁺+1)

Example 789 N1-(4-Chlorophenyl)-2-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenoxy}acetamide

2-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenoxy}acetic acid (150 mg), WSC.HCl (122 mg), and HOBT.H₂O (86 mg) were dissolved in chloroform (5 ml) to prepare a solution. 4-Chloroaniline (65 mg) was then added to the solution, and the mixture was heated under reflux for 5 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was washed with 1 N hydrochloric acid, water, and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (156 mg, yield 79%).

The resultant compound (49 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 39 mg of a hydrochloride.

Mass spectrometry value (ESI-MS, m/z): 465 (M⁺+1)

Example 790 6,7-Dimethoxy-4-{4-[3-(4-methylphenoxy)propoxy]phenoxy}quinoline

p-Cresol (300 mg) was dissolved in acetone (5 ml) to prepare a solution. 1,3-Dibromopropane (0.85 ml), potassium carbonate (765 mg), and tetra-n-butylammonium iodide (102 mg) were then added to the solution, and the mixture was heated under reflux for 3 hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropyl)-4-methylbenzene (1) (466 mg, yield 74%).

4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenol (100 mg) was dissolved in dimethylformamide (2 ml) to prepare a solution. Sodium hydride (16 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. A solution of the compound (1) (85 mg) in dimethylformamide was added thereto, and the mixture was further stirred at room temperature for 4 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing three times with saturated brine. The extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (142 mg, yield 95%).

The resultant compound (138 mg) was dissolved in a 10% hydrochloric acid-methanol solution (5 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 117 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.16-2.22 (m, 2H), 2.23 (s, 3H), 4.03 (s, 3H), 4.04 (s, 3H), 4.12 (t, J=6.1 Hz, 2H), 4.20 (t, J=6.1 Hz, 2H), 6.80 (d, J=6.3 Hz, 1H), 6.83-6.88 (m, 2H), 7.09 (d, J=8.5 Hz, 2H), 7.14-7.20 (m, 2H), 7.31-7.36 (m, 2H), 7.59 (s, 1H), 7.74 (s, 1H), 8.77 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 446 (M⁺+1)

Example 791 6,7-Dimethoxy-4-{4-[3-(3-methylphenoxy)propoxy]phenoxy}quinoline

m-Cresol (300 mg) was dissolved in acetone (5 ml) to prepare a solution. 1,3-Dibromopropane (0.85 ml), potassium carbonate (765 mg), and tetra-n-butylammonium iodide (102 mg) were then added to the solution, and the mixture was heated under reflux for 3 hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropyl)-3-methylbenzene (1) (490 mg, yield 78%).

4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenol (100 mg) was dissolved in dimethylformamide (2 ml) to prepare a solution. Sodium hydride (16 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. A solution of the compound (1) (85 mg) in dimethylformamide was added thereto, and the mixture was further stirred at room temperature for 4 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing three times with saturated brine. The extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (145 mg, yield 97%).

The resultant compound (139 mg) was dissolved in a 10% hydrochloric acid-methanol solution (5 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 103 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.16-2.24 (m, 2H), 2.28 (s, 3H), 4.03 (s, 3H), 4.04 (s, 3H), 4.14 (t, J=6.3 Hz, 2H), 4.20 (t, J=6.1 Hz, 2H), 6.74-6.81 (m, 4H), 7.14-7.20 (m, 3H), 7.32-7.37 (m, 2H), 7.58 (s, 1H), 7.74 (s, 1H), 8.77 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 446 (M⁺+1)

Example 792 6,7-Dimethoxy-4-{4-[3-(2-methyl-phenoxy)propoxy]phenoxy}quinoline

o-Cresol (300 mg) was dissolved in acetone (5 ml) to prepare a solution. 1,3-Dibromopropane (0.85 ml), potassium carbonate (765 mg), and tetra-n-butylammonium iodide (102 mg) were added to the solution, and the mixture was heated under reflux for 4 hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropyl)-2-methylbenzene (1) (363 mg, yield 57%).

4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenol (100 mg) was dissolved in dimethylformamide (2 ml) to prepare a solution. Sodium hydride (16 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. A solution of the compound (1) (85 mg) in dimethylformamide was added thereto, and the mixture was further stirred at room temperature for 2 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing three times with saturated brine. The extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (148 mg, yield 98%).

The resultant compound (145 mg) was dissolved in a 10% hydrochloric acid-methanol solution (5 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 106 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.17 (s, 3H), 2.20-2.26 (m, 2H), 4.04 (s, 3H), 4.05 (s, 3H), 4.16 (t, J=6.1 Hz, 2H), 4.24 (t, J=6.1 Hz, 2H), 6.80-6.87 (m, 2H), 6.96 (d, J=7.8 Hz, 1H), 7.12-7.21 (m, 4H), 7.33-7.38 (m, 2H), 7.69 (s, 1H), 7.75 (s, 1H), 8.81 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 446 (M⁺+1)

Example 793 6,7-Dimethoxy-4-{4-[3-(3-methoxyphenoxy)propoxy]phenoxy}quinoline

3-Methoxyphenol (300 mg) was dissolved in acetone (5 ml) to prepare a solution. 1,3-Dibromopropane (0.74 ml), potassium carbonate (668 mg), and tetra-n-butylammonium iodide (89 mg) were added to the solution, and the mixture was heated under reflux for 4 hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropyl)-3-methoxybenzene (1) (440 mg, yield 74%).

4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenol (100 mg) was dissolved in dimethylformamide (2 ml) to prepare a solution. Sodium hydride (16 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. A solution of the compound (1) (91 mg) in dimethylformamide was added thereto, and the mixture was further stirred at room temperature for 2 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing three times with saturated brine. The extract was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (147 mg, yield 95%).

The resultant compound (143 mg) was dissolved in a 10% hydrochloric acid-methanol solution (5 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 109 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.17-2.24 (m, 2H), 3.73 (s, 3H), 4.03 (s, 3H), 4.04 (s, 3H), 4.15 (t, J=6.1 Hz, 2H), 4.20 (t, J=6.1 Hz, 2H), 6.51-6.57 (m, 3H), 6.80 (d, J=6.8 Hz, 1H), 7.15-7.21 (m, 3H), 7.32-7.37 (m, 2H), 7.64 (s, 1H), 7.74 (s, 1H), 8.77 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 462 (M⁺+1)

Example 794 6,7-Dimethoxy-4-{4-[3-(4-methoxyphenoxy)propoxy]phenoxy}quinoline

4-Methoxyphenol (300 mg) was dissolved in acetone (5 ml) to prepare a solution. 1,3-Dibromopropane (0.74 ml), potassium carbonate (668 mg), and tetra-n-butylammonium iodide (89 mg) were then added to the solution, and the mixture was heated under reflux for 7 hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropyl)-4-methoxybenzene (1) (399 mg, yield 67%).

4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenol (100 mg) was dissolved in dimethylformamide (2 ml) to prepare a solution. Sodium hydride (16 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. A solution of the compound (1) (91 mg) in dimethylformamide was added thereto, and the mixture was further stirred at room temperature for 6 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing three times with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (150 mg, yield 97%).

The resultant compound (141 mg) was dissolved in a 10% hydrochloric acid-methanol solution (5 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 135 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.15-2.23 (m, 2H), 3.70 (s, 3H), 4.03 (s, 3H), 4.04 (s, 3H), 4.10 (t, J=6.3 Hz, 2H), 4.20 (t, J=6.1 Hz, 2H), 6.80 (d, J=6.6 Hz, 1H), 6.84-6.93 (m, 4H), 7.15-7.20 (m, 2H), 7.32-7.37 (m, 2H), 7.64 (s, 1H), 7.74 (s, 1H), 8.77 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 462 (M⁺+1)

Example 795 6,7-Dimethoxy-4-{4-[3-(2-methoxyphenoxy)propoxy]phenoxy}quinoline

Guaiacol (300 mg) was dissolved in acetone (5 ml) to prepare a solution. 1,3-Dibromopropane (0.74 ml), potassium carbonate (668 mg), and tetra-n-butylammonium iodide (89 mg) were then added to the solution, and the mixture was heated under reflux for 7 hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropyl)-2-methoxybenzene (1) (449 mg, yield 76%).

4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenol (100 mg) was dissolved in dimethylformamide (2 ml) to prepare a solution. Sodium hydride (16 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. A solution of the compound (1) (91 mg) in dimethylformamide was added thereto, and the mixture was further stirred at room temperature for 6 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing three times with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (116 mg, yield 75%).

The resultant compound (103 mg) was dissolved in a 10% hydrochloric acid-methanol solution (5 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 86 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.17-2.24 (m, 2H), 3.76 (s, 3H), 4.03 (s, 3H), 4.04 (s, 3H), 4.14 (t, J=6.1 Hz, 2H), 4.21 (t, J=6.1 Hz, 2H), 6.79 (d, J=6.6 Hz, 1H), 6.86-7.03 (m, 4H), 7.15-7.20 (m, 2H), 7.32-7.37 (m, 2H), 7.66 (s, 1H), 7.74 (s, 1H), 8.76 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 462 (M⁺+1)

Example 796 4-{4-[3-(2-Fluorophenoxy)propoxy]-phenoxy}-6,7-dimethoxyquinoline

o-Fluorophenol (400 mg) was dissolved in acetone (5 ml) to prepare a solution. 1,3-Dibromopropane (1.09 ml), potassium carbonate (985 mg), and tetra-n-butylammonium iodide (132 mg) were then added to the solution, and the mixture was heated under reflux for 3 hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropyl)-2-fluorobenzene (1) (750 mg, yield 91%).

4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenol (100 mg) was dissolved in dimethylformamide (2 ml) to prepare a solution. Sodium hydride (16 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. A solution of the compound (1) (86 mg) in dimethylformamide was added thereto, and the mixture was further stirred at room temperature for 5 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing three times with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (131 mg, yield 78%).

The resultant compound (128 mg) was dissolved in a 10% hydrochloric acid-methanol solution (5 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 116 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.21-2.27 (m, 2H), 4.03 (s, 3H), 4.04 (s, 3H), 4.19-4.27 (m, 4H), 6.81 (d, J=6.6 Hz, 1H), 6.92-6.98 (m, 1H), 7.11-7.25 (m, 5H), 7.33-7.37 (m, 2H), 7.63-7.69 (m, 1H), 7.75 (s, 1H), 8.78 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 450 (M⁺+1)

Example 797 4-{4-[3-(3-Fluorophenoxy)propoxy]-phenoxy}-6,7-dimethoxyquinoline

3-Fluorophenol (400 mg) was dissolved in acetone (5 ml) to prepare a solution. 1,3-Dibromopropane (1.09 ml), potassium carbonate (985 mg), and tetra-n-butylammonium iodide (132 mg) were then added to the solution, and the mixture was heated under reflux for 3 hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropyl)-3-fluorobenzene (1) (808 mg, yield 97%).

4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenol (100 mg) was dissolved in dimethylformamide (2 ml) to prepare a solution. Sodium hydride (16 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. A solution of the compound (1) (86 mg) in dimethylformamide was added thereto, and the mixture was further stirred at room temperature for 5 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing three times with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (128 mg, yield 84%).

The resultant compound (123 mg) was dissolved in a 10% hydrochloric acid-methanol solution (5 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 109 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.18-2.25 (m, 2H), 4.04 (s, 3H), 4.05 (s, 3H), 4.17-4.22 (m, 4H), 6.74-6.88 (m, 4H), 7.15-7.20 (m, 2H), 7.29-7.38 (m, 3H), 7.61-7.73 (m, 1H), 7.76 (s, 1H), 8.79 (d, J=6.8 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 450 (M⁺+1)

Example 798 4-{4-[3-(4-Fluorophenoxy)propoxy]-phenoxy}-6,7-dimethoxyquinoline

4-Fluorophenol (400 mg) was dissolved in acetone (5 ml) to prepare a solution. 1,3-Dibromopropane (1.09 ml), potassium carbonate (985 mg), and tetra-n-butylammonium iodide (132 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropyl)-4-fluorobenzene (1) (713 mg, yield 86%).

4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenol (100 mg) was dissolved in dimethylformamide (2 ml) to prepare a solution. Sodium hydride (16 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. A solution of the compound (1) (86 mg) in dimethylformamide was added thereto, and the mixture was further stirred at room temperature for 4 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing three times with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (91 mg, yield 60%).

The resultant compound (85 mg) was dissolved in a 10% hydrochloric acid-methanol solution (5 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 90 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.16-2.24 (m, 2H), 4.04 (s, 3H), 4.05 (s, 3H), 4.14 (t, J=6.1 Hz, 2H), 4.20 (t, J=6.1 Hz, 2H), 6.82 (d, J=6.6 Hz, 1H), 6.95-7.01 (m, 2H), 7.09-7.20 (m, 4H), 7.33-7.37 (m, 2H), 7.67 (s, 1H), 7.75 (s, 1H), 8.79 (d, J=6.8 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 450 (M⁺+1)

Example 799 4-{4-[3-(2,6-Dimethylphenoxy)propoxy]-phenoxy}-6,7-dimethoxyquinoline

2,6-Dimethylphenol (400 mg) was dissolved in acetone (5 ml) to prepare a solution. 1,3-Dibromopropane (1.00 ml), potassium carbonate (903 mg), and tetra-n-butylammonium iodide (121 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropyl)-2,6-dimethylbenzene (1) (637 mg, yield 81%).

4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenol (100 mg) was dissolved in dimethylformamide (2 ml) to prepare a solution. Sodium hydride (16 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. A solution of the compound (1) (90 mg) in dimethylformamide was added thereto, and the mixture was further stirred at room temperature for 4 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing three times with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (137 mg, yield 88%).

The resultant compound (116 mg) was dissolved in a 10% hydrochloric acid-methanol solution (5 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 75 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.21 (s, 6H), 2.22 (t, J=6.1 Hz, 2H), 3.92 (t, J=6.1 Hz, 2H), 4.04 (s, 3H), 4.04 (s, 3H), 4.29 (t, J=6.1 Hz, 2H), 6.80 (d, J=6.6 Hz, 1H), 6.89-6.94 (m, 1H), 7.01 (s, 1H), 7.03 (s, 1H), 7.17-7.22 (m, 2H), 7.34-7.39 (m, 2H), 7.70 (s, 1H), 7.75 (s, 1H), 8.80 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 460 (M⁺+1)

Example 800 N1-(3-Methoxyphenyl)-2-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenoxy}acetamide

2-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenoxy}-acetic acid (150 mg), WSC.HCl (122 mg), and HOBT.H₂O (86 mg) were dissolved in chloroform (5 ml) to prepare a solution. m-Anisidine (63 mg) was then added to the solution, and the mixture was stirred at room temperature for 4 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was washed with 1 N hydrochloric acid, water, and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (29 mg, yield 15%).

¹H-NMR (chloroform-d, 400 MHz): δ 3.84 (s, 3H), 4.08 (s, 3H), 4.08 (s, 3H), 4.65 (s, 2H), 6.71-6.75 (m, 1H), 7.07-7.13 (m, 3H), 7.24-7.28 (m, 2H), 7.35 (t, J=2.2 Hz, 1H), 7.40 (s, 1H), 7.56 (s, 1H), 8.25 (s, 1H), 8.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 462 (M⁺+1)

Example 801 N1-(3-Methoxybenzyl)-2-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenoxy}acetamide

2-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenoxy}-acetic acid (150 mg), WSC.HCl (122 mg), and HOBT.H₂O (86 mg) were dissolved in chloroform (5 ml) to prepare a solution. 3-Methoxybenzylamine (70 mg) was then added to the solution, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was washed with 1 N hydrochloric acid, water, and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (31 mg, yield 16%).

¹H-NMR (chloroform-d, 400 MHz): δ 3.81 (s, 3H), 4.07 (s, 6H), 4.54 (s, 1H), 4.56 (s, 1H), 4.60 (s, 2H), 6.82-6.93 (m, 3H), 6.99-7.05 (m, 2H), 7.19-7.23 (m, 2H), 7.27-7.31 (m, 1H), 7.35 (s, 1H), 7.55 (s, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 476 (M⁺+1)

Example 802 2-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenoxy}-1-(1,2,3,4-tetrahydro-2-isoquinolyl)-1-ethanone

2-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenoxy}-acetic acid (100 mg), WSC.HCl (81 mg), and HOBT.H₂O (57 mg) were dissolved in chloroform (3 ml) to prepare a solution. 1,2,3,4-Tetrahydro-isoquinoline (45 mg) was then added to the solution, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (39 mg, yield 30%).

¹H-NMR (chloroform-d, 400 MHz): δ 2.88-2.98 (m, 2H), 3.80-3.90 (m, 2H), 4.07 (s, 3H), 4.07 (s, 3H), 4.76 (s, 1H), 4.78 (s, 1H), 4.80 (s, 2H), 7.04-7.24 (m, 8H), 7.35 (s, 1H), 7.55 (s, 1H), 8.63 (d, J=3.7 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 472 (M⁺+1)

Example 803 2-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenoxy}-1-(4-phenylpiperidino)-1-ethanone

2-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenoxy}-acetic acid (100 mg), WSC.HCl (81 mg), and HOBT.H₂O (57 mg) were dissolved in chloroform (3 ml) to prepare a solution. 4-Phenylpiperidine (54 mg) was then added to the solution, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (42 mg, yield 30%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.61-1.73 (m, 2H), 1.90-2.00 (m, 2H), 2.68-2.83 (m, 2H), 3.16-3.26 (m, 1H), 4.08 (s, 3H), 4.14 (s, 3H), 4.08-4.20 (m, 2H), 4.76 (s, 1H), 4.77 (s, 1H), 7.06-7.12 (m, 2H), 7.17-7.34 (m, 7H), 7.39 (s, 1H), 7.56 (s, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 500 (M⁺+1)

Example 804 1-(4-Benzylpiperidino)-2-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenoxy}-1-ethanone

2-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenoxy}-acetic acid (100 mg), WSC.HCl (81 mg), and HOBT.H₂O (57 mg) were dissolved in chloroform (3 ml) to prepare a solution. 4-Benzylpiperidine (59 mg) was then added to the solution, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (36 mg, yield 25%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.15-1.30 (m, 2H), 1.73 (d, J=13.7 Hz, 2H), 1.76-1.88 (m, 1H), 2.53-2.66 (m, 3H), 2.98-3.09 (m, 1H), 3.94-4.02 (m, 1H), 4.09 (s, 3H), 4.12 (s, 3H), 4.54-4.62 (m, 1H), 4.71 (s, 2H), 7.03-7.10 (m, 2H), 7.12-7.24 (m, 5H), 7.25-7.33 (m, 2H), 7.58 (s, 1H), 7.63 (s, 1H), 8.69 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 514 (M⁺+1)

Example 805 2-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenoxy}-1-(4-piperidinopiperidino)-1-ethanone

2-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenoxy}-acetic acid (100 mg), WSC.HCl (81 mg), and HOBT.H₂O (57 mg) were dissolved in chloroform (3 ml) to prepare a solution. 4-Piperidinopiperidine (57 mg) was then added to the solution, and the mixture was stirred at room temperature overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (34 mg, yield 24%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.42-2.08 (m, 10H), 2.58-2.90 (m, 5H), 3.05-3.15 (m, 1H), 4.07 (s, 6H), 4.12-4.20 (m, 1H), 4.65-4.72 (m, 1H), 4.71 (s, 1H), 4.73 (s, 1H), 7.02-7.08 (m, 2H), 7.16-7.22 (m, 2H), 7.32 (s, 1H), 7.55 (s, 1H), 8.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 507 (M⁺+1)

Example 806 2-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenoxy}-1-piperidino-1-ethanone

2-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenoxy}-acetic acid (100 mg), WSC.HCl (81 mg), and HOBT.H₂O (57 mg) were dissolved in chloroform (3 ml) to prepare a solution. Piperidine (29 mg) was then added to the solution, and the mixture was stirred at room temperature for 3 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (31 mg, yield 26%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.54-1.90 (m, 6H), 3.49-3.61 (m, 4H), 4.07 (s, 3H), 4.08 (s, 3H), 4.71 (s, 2H), 7.04-7.09 (m, 2H), 7.16-7.20 (m, 2H), 7.40 (s, 1H), 7.56 (s, 1H), 8.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 424 (M⁺+1)

Example 807 N-(2-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenoxy}ethyl)-N,N-diethylamine

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenol (100 mg) was dissolved in dimethylformamide (2 ml) to prepare a solution. Sodium hydride (27 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. 2-(Diethylamino)ethyl bromide hydrobromide (88 mg) was added to the solution, and the mixture was stirred at room temperature for 2 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (30 mg, yield 23%).

¹H-NMR (chloroform-d, 400 MHz): δ 1.20-1.44 (m, 6H), 2.80-3.15 (m, 4H), 3.15-3.30 (m, 2H), 4.07 (s, 3H), 4.07 (s, 3H), 4.27-4.45 (m, 2H), 6.98-7.03 (m, 2H), 7.16-7.20 (m, 2H), 7.32 (s, 1H), 7.56 (s, 1H), 8.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 398 (M⁺+1)

Example 808 4-{4-[3-(4-Fluorophenoxy)propoxy]-phenoxy}-6,7-dimethoxyquinazoline

4-Fluorophenol (1 g) was dissolved in acetone (10 ml) to prepare a solution. 1,3-Dibromopropane (2.72 ml), potassium carbonate (2.46 g), and tetra-n-butylammonium iodide (329 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropyl)-4-fluorobenzene (1) (1.89 g, yield 91%).

4-Hydroxyphenyl benzoate (300 mg) was dissolved in dimethylformamide (2 ml) to prepare a solution. Sodium hydride (84 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. A solution of the compound (1) (650 mg) in dimethylformamide was added thereto, and the mixture was further stirred at room temperature for one hr. A saturated aqueous ammonium chloride solution was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing three times with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give 4-[3-(4-fluorophenoxy)propoxy]phenyl benzoate (2) (412 mg, yield 81%).

The compound (2) (412 mg) was dissolved in methanol (3 ml) to prepare a solution. Sodium hydroxide (60 mg) was added to the solution, and the mixture was stirred at room temperature for 3 hr. A saturated aqueous ammonium chloride solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using hexane/acetone for development to give 4-[3-(4-fluorophenoxy)propoxy]phenol (3) (229 mg, yield 78%).

Chlorobenzene (0.4 ml) was added to the compound (3) (225 mg) and 4-chloro-6,7-dimethoxyquinazoline (275 mg), and the mixture was stirred at 140° C. overnigh. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (117 mg, yield 31%).

¹H-NMR (chloroform-d, 400 MHz): δ 2.24-2.31 (m, 2H), 4.07 (s, 6H), 4.14 (t, J=6.1 Hz, 2H), 4.19 (t, J=6.1 Hz, 2H), 6.83-6.88 (m, 2H), 6.94-7.03 (m, 4H), 7.14-7.19 (m, 2H), 7.33 (s, 1H), 7.56 (s, 1H), 8.63 (s, 1H)

Mass spectrometry value (FD-MS, m/z): 450 (M⁺)

Example 809 6,7-Dimethoxy-4-{4-[3-(3-methoxyphenoxy)propoxy]phenoxy}quinazoline

3-Methoxyphenol (1 g) was dissolved in acetone (10 ml) to prepare a solution. 1,3-Dibromopropane (2.45 ml), potassium carbonate (2.22 g), and tetra-n-butylammonium iodide (297 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropyl)-3-methoxybenzene (1) (1.79 g, yield 91%).

4-Hydroxyphenyl benzoate (300 mg) was dissolved in dimethylformamide (2 ml) to prepare a solution. Sodium hydride (84 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. A solution of the compound (1) (686 mg) in dimethylformamide was added thereto, and the mixture was further stirred at room temperature for one hr. A saturated aqueous ammonium chloride solution was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing three times with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give 4-[3-(3-methoxyphenoxy)propoxy]-phenyl benzoate (2) (252 mg, yield 48%).

The compound (2) (252 mg) was dissolved in methanol (2 ml) to prepare a solution. Sodium hydroxide (60 mg) was then added to the solution, and the mixture was stirred at room temperature for 3 hr. A saturated aqueous ammonium chloride solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give 4-[3-(3-methoxyphenoxy)propoxy]phenol (3) (146 mg, yield 80%).

Chlorobenzene (0.4 ml) was added to the compound (3) (143 mg) and 4-chloro-6,7-dimethoxyquinazoline (167 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (118 mg, yield 50%).

¹H-NMR (chloroform-d, 400 MHz): δ 2.24-2.32 (m, 2H), 3.80 (s, 3H), 4.07 (s, 6H), 4.15-4.22 (m, 4H), 6.48-6.55 (m, 3H), 6.98-7.03 (m, 2H), 7.14-7.21 (m, 3H), 7.35 (s, 1H), 7.56 (s, 1H), 8.63 (s, 1H)

Mass spectrometry value (FD-MS, m/z): 462 (M⁺)

Example 810 6,7-Dimethoxy-4-{4-[3-(2-methoxyphenoxy)propoxy]phenoxy}quinazoline

2-Methoxyphenol (750 mg) was dissolved in acetonitrile (8 ml) to prepare a solution. 1,3-Dibromopropane (0.92 ml) and potassium carbonate (1.25 g) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropyl)-2-methoxybenzene (1).

4-Hydroxyphenyl benzoate (650 mg) was dissolved in dimethylformamide (6 ml) to prepare a solution. Sodium hydride (97 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. A solution of the compound (1) (1.12 g) in dimethylformamide was added thereto, and the mixture was further stirred at room temperature for one hr. A saturated aqueous ammonium chloride solution was added to the reaction solution, and the mixture was extracted with ethyl acetate, followed by washing three times with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give 4-[3-(2-methoxyphenoxy)propoxy]-phenyl benzoate (2) (1.15 g, yield 50%).

The compound (2) (1.15 g) was dissolved in methanol (10 ml) to prepare a solution. Sodium hydroxide (20 mg) was added to the solution, and the mixture was stirred at room temperature for 3 hr. A saturated aqueous ammonium chloride solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give 4-[3-(2-methoxyphenoxy)propoxy]phenol (3) (0.55 g, yield 66%).

Chlorobenzene (0.4 ml) was added to the compound (3) (205 mg) and 4-chloro-6,7-dimethoxyquinazoline (252 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (128 mg, yield 37%).

¹H-NMR (chloroform-d, 400 MHz): δ 2.30-2.38 (m, 2H), 3.87 (s, 3H), 4.08 (s, 3H), 4.09 (s, 3H), 4.21-4.26 (m, 4H), 6.88-6.96 (m, 4H), 6.99-7.03 (m, 2H), 7.13-7.17 (m, 2H), 7.47 (s, 1H), 7.57 (s, 1H), 8.66 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 463 (M⁺+1)

The resultant compound (125 mg) was dissolved in a 10% hydrochloric acid-methanol solution (6 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 61 mg of a hydrochloride.

Example 811 4-{4-[3-(1H-1-Indolyl)propoxy]-phenoxy}-6,7-dimethoxyquinazoline

Dimethyl sulfoxide (25 ml) was added to potassium hydroxide (2.18 g), and the mixture was stirred. A solution of indole (3 g) in dimethyl sulfoxide was added drowise thereto, and the mixture was stirred at room temperature for 10 min. 3-Bromo-1-propanol (2.31 ml) was added thereto, and the mixture was stirred at room temperature for 5 hr. Water was added to the reaction solution, and the mixture was extrated with ethyl acetate, followed by washing three times with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give 1-(3-bromopropyl)-1H-indole (1) (3.78 g, yield 84%).

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenol (100 mg), the compound (1) (59 mg), and triphenylphosphine (106 mg) were dissolved in tetrahydrofuran (3 ml) to prepare a solution. Diethyl azodicarboxylate (0.063 ml) was then added to the solution, and the mixture was stirred at room temperature for 3 hr. The solvent was removed by distillation under the reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using hexane/acetone for development. Diethyl ether was added to the purification product, and the precipitated crystal was collected by filtration and was washed to give the title compound (3 mg, yield 2%).

Mass spectrometry value (FD-MS, m/z): 455 (M⁺)

Example 812 6,7-Dimethoxy-4-(4-{[2-(3-methoxyphenoxy)ethyl]sulfanyl}phenoxy)quinoline

3-Methoxyphenol (0.6 g) was dissolved in acetone (2 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.60 ml), potassium carbonate (1.00 g), and tetra-n-butylammonium iodide (180 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-chloroethoxy)-3-methoxybenzene (1) (348 mg, yield 39%).

The compound (1) (206 mg) was dissolved in acetone (1 ml) to prepare a solution. 4-Hydroxythiophenol (160 mg) and potassium carbonate (168 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(3-methoxyphenoxy)ethyl]sulfanyl}phenol (2) (116 mg, yield 38%).

Chlorobenzene (0.2 ml) was added to the compound (2) (105 mg) and 4-chloro-6,7-dimethoxyquinoline (170 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (26 mg, yield 15%).

The resultant compound (20 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 15 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 17 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.41 (t, J=6.3 Hz, 2H), 3.72 (s, 3H), 4.01 (s, 3H), 4.03 (s, 3H), 4.19 (t, J=6.3 Hz, 2H), 6.44-6.55 (m, 3H), 6.85 (d, J=6.6 Hz, 1H), 7.18 (t, J=8.1 Hz, 1H), 7.36-7.41 (m, 2H), 7.60 (s, 1H), 7.61-7.65 (m, 2H), 7.72 (s, 1H), 8.77 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 464 (M⁺+1)

Example 813 6,7-Dimethoxy-4-(4-{[2-(4-methoxyphenoxy)ethyl]sulfanyl}phenoxy)quinoline

4-Methoxyphenol (0.6 g) was dissolved in acetone (2 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.60 ml), potassium carbonate (1.00 g), and tetra-n-butylammonium iodide (180 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-chloroethoxy)-4-methoxybenzene (1) (246 mg, yield 27%).

The compound (1) (226 mg) was dissolved in acetone (2 ml) to prepare a solution. 4-Hydroxythiophenol (170 mg) and potassium carbonate (184 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(4-methoxyphenoxy)ethyl]sulfanyl}phenol (2) (114 mg, yield 34%).

Chlorobenzene (0.3 ml) was added to the compound (2) (102 mg) and 4-chloro-6,7-dimethoxyquinoline (165 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (80 mg, yield 47%).

The resultant compound (66 mg) was dissolved in a 10% hydrochloric acid-methanol solution (6 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 51 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.39-3.42 (m, 2H), 3.68 (s, 3H), 4.00 (s, 3H), 4.03 (s, 3H), 4.13 (t, J=6.1 Hz, 2H), 6.81-6.84 (m, 1H), 6.85 (s, 2H), 6.85 (s, 2H), 7.33-7.39 (m, 2H), 7.53 (s, 1H), 7.57-7.63 (m, 2H), 7.70 (s, 1H), 8.75 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 464 (M⁺+1)

Example 814 6,7-Dimethoxy-4-(4-{[2-(4-methylphenoxy)ethyl]sulfanyl}phenoxy)quinoline

p-Cresol (0.6 g) was dissolved in acetone (2 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.69 ml), potassium carbonate (1.15 g), and tetra-n-butylammonium iodide (205 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-chloroethoxy)-4-methylbenzene (1) (348 mg, yield 37%).

The compound (1) (326 mg) was dissolved in acetone (2 ml) to prepare a solution. 4-Hydroxythiophenol (265 mg) and potassium carbonate (290 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(4-methylphenoxy)ethyl]sulfanyl}phenol (2) (185 mg, yield 37%).

Chlorobenzene (0.5 ml) was added to the compound (2) (170 mg) and 4-chloro-6,7-dimethoxyquinoline (292 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (124 mg, yield 42%).

The resultant compound (124 mg) was dissolved in a 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 105 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.21 (s, 3H), 3.39-3.42 (m, 2H), 4.01 (s, 3H), 4.03 (s, 3H), 4.15 (t, J=6.1 Hz, 2H), 6.77-6.83 (m, 2H), 6.86 (d, J=6.6 Hz, 1H), 7.04-7.10 (m, 2H), 7.34-7.40 (m, 2H), 7.56 (s, 1H), 7.57-7.64 (m, 2H), 7.72 (s, 1H), 8.77 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 4.48 (M⁺+1)

Example 815 4-(4-{[2-(2-Isopropylphenoxy)ethyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinoline

2-Isopropylphenol (1 g) was dissolved in acetone (3 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.92 ml), potassium carbonate (1.52 g), and tetra-n-butylammonium iodide (271 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-chloroethoxy)-2-isopropylbenzene (1) (480 mg, yield 33%).

The compound (1) (438 mg) was dissolved in acetone (3 ml) to prepare a solution. 4-Hydroxythiophenol (306 mg) and potassium carbonate (335 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(2-isopropylphenoxy)ethyl]sulfanyl}phenol (2) (288 mg, yield 46%).

Chlorobenzene (0.5 ml) was added to the compound (2) (252 mg) and 4-chloro-6,7-dimethoxyquinoline (390 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (183 mg, yield 44%).

The resultant compound (123 mg) was dissolved in a 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 91 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.16 (s, 3H), 1.18 (s, 3H), 3.19-3.26 (m, 1H), 3.48 (t, J=6.1 Hz, 2H), 4.02 (s, 3H), 4.04 (s, 3H), 4.22 (t, J=6.1 Hz, 2H), 6.85 (d, J=6.4 Hz, 1H), 6.89-6.95 (m, 2H), 7.10-7.22 (m, 2H), 7.35-7.41 (m, 2H), 7.59-7.65 (m, 3H), 7.72 (s, 1H), 8.78 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 476 (M⁺+1)

Example 816 4-(4-{[2-(4-Isopropylphenoxy)ethyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinoline

4-Isopropylphenol (1 g) was dissolved in acetone (3 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.92 ml), potassium carbonate (1.52 g), and tetra-n-butylammonium iodide (271 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-chloroethoxy)-4-isopropylbenzene (1) (616 mg, yield 42%).

The compound (1) (590 mg) was dissolved in acetone (4 ml) to prepare a solution. 4-Hydroxythiophenol (412 mg) and potassium carbonate (452 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(4-isopropylphenoxy)-ethyl]sulfanyl}phenol (2) (441 mg, yield 52%).

Chlorobenzene (0.8 ml) was added to the compound (2) (394 mg) and 4-chloro-6,7-dimethoxyquinoline (610 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (289 mg, yield 44%).

The resultant compound (217 mg) was dissolved in a 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 195 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.16 (s, 3H), 1.17 (s, 3H), 2.78-2.87 (m, 1H), 3.43 (t, J=6.3 Hz, 2H), 4.03 (s, 3H), 4.05 (s, 3H), 4.18 (t, J=6.3 Hz, 2H), 6.82-6.87 (m, 2H), 6.89 (d, J=6.6 Hz, 1H), 7.12-7.17 (m, 2H), 7.38-7.43 (m, 2H), 7.61-7.66 (m, 2H), 7.69 (s, 1H), 7.74 (s, 1H), 8.80 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 476 (M⁺+1)

Example 817 6,7-Dimethoxy-4-(4-{[2-(2-methylphenoxy)ethyl]sulfanyl}phenoxy)quinoline

o-Cresol (0.6 g) was dissolved in acetone (2 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.69 ml), potassium carbonate (1.15 g), and tetra-n-butylammonium iodide (205 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-chloroethoxy)-2-methylbenzene (1) (345 mg, yield 36%).

The compound (1) (322 mg) was dissolved in acetone (2 ml) to prepare a solution. 4-Hydroxythiophenol (262 mg) and potassium carbonate (286 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(2-methylphenoxy)ethyl]-sulfanyl}phenol (2) (231 mg, yield 47%).

Chlorobenzene (0.3 ml) was added to the compound (2) (204 mg) and 4-chloro-6,7-dimethoxyquinoline (350 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (139 mg, yield 40%).

The resultant compound (103 mg) was dissolved in a 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 26 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.13 (s, 3H), 3.47 (t, J=6.1 Hz, 2H), 4.02 (s, 3H), 4.04 (s, 3H), 4.22 (t, J=5.9 Hz, 2H), 6.81-6.94 (m, 3H), 7.11-7.17 (m, 2H), 7.35-7.40 (m, 2H), 7.59 (s, 1H), 7.60-7.66 (m, 2H), 7.72 (s, 1H), 8.78 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 448 (M⁺+1)

Example 818 4-(4-{[2-(4-Chlorophenoxy)ethyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinoline

p-Chlorophenol (0.6 g) was dissolved in acetone (2 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.58 ml), potassium carbonate (967 mg), and tetra-n-butylammonium iodide (173 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-chloro-4-(2-chloroethoxy)-benzene (1) (338 mg, yield 38%).

The compound (1) (338 mg) was dissolved in acetone (3 ml) to prepare a solution. 4-Hydroxythiophenol (246 mg) and potassium carbonate (270 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(4-chlorophenoxy)ethyl]sulfanyl}phenol (2) (265 mg, yield 53%).

Chlorobenzene (0.4 ml) was added to the compound (2) (215 mg) and 4-chloro-6,7-dimethoxyquinoline (343 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (5 mg, yield 1%).

The resultant compound (5 mg) was dissolved in a 10% hydrochloric acid-methanol solution (2 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 6 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.44 (t, J=6.3 Hz, 2H), 4.02 (s, 3H), 4.04 (s, 3H), 4.21 (t, J=6.1 Hz, 2H), 6.85 (d, J=6.3 Hz, 1H), 6.93-6.99 (m, 2H), 7.30-7.35 (m, 2H), 7.38 (s, 1H), 7.40 (s, 1H), 7.60-7.65 (m, 3H), 7.72 (s, 1H), 8.78 (d, J=6.6 Hz, 1H)

Example 819 4-(4-{[2-(2-Chlorophenoxy)ethyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinoline

2-Chlorophenol (0.6 g) was dissolved in acetone (2 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.58 ml), potassium carbonate (967 mg), and tetra-n-butylammonium iodide (173 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-chloro-2-(2-chloroethoxy)-benzene (1) (429 mg, yield 48%).

The compound (1) (412 mg) was dissolved in acetone (4 ml) to prepare a solution. 4-Hydroxythiophenol (300 mg) and potassium carbonate (328 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(2-chlorophenoxy)ethyl]sulfanyl}phenol (2) (449 mg, yield 74%).

Chlorobenzene (0.4 ml) was added to the compound (2) (320 mg) and 4-chloro-6,7-dimethoxyquinoline (510 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (2 mg, yield 0.3%).

The resultant compound (2 mg) was dissolved in a 10% hydrochloric acid-methanol solution (2 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 2 mg of a hydrochloride.

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 820 4-(4-{[2-(3-Chlorophenoxy)ethyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinoline

3-Chlorophenol (0.6 g) was dissolved in acetone (2 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.58 ml), potassium carbonate (967 mg), and tetra-n-butylammonium iodide (173 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-chloro-3-(2-chloroethoxy)-benzene (1) (400 mg, yield 45%).

The compound (1) (387 mg) was dissolved in acetone (4 ml) to prepare a solution. 4-Hydroxythiophenol (281 mg) and potassium carbonate (308 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(3-chlorophenoxy)ethyl]sulfanyl}phenol (2) (322 mg, yield 57%).

Chlorobenzene (0.4 ml) was added to the compound (2) (206 mg) and 4-chloro-6,7-dimethoxyquinoline (328 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (105 mg, yield 31%).

The resultant compound (93 mg) was dissolved in a 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 81 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.43 (t, J=6.3 Hz, 2H), 4.02 (s, 3H), 4.04 (s, 3H), 4.24 (t, J=6.1 Hz, 2H), 6.83-7.03 (m, 4H), 7.28-7.41 (m, 3H), 7.60-7.65 (m, 3H), 7.72 (s, 1H), 8.78 (d, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 821 4-(4-{[2-(3-Fluorophenoxy)ethyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinoline

3-Fluorophenol (0.6 g) was dissolved in acetone (2 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.67 ml), potassium carbonate (1.11 g), and tetra-n-butylammonium iodide (198 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-2-5 chloroethoxy)-3-fluorobenzene (1) (407 mg, yield 44%).

The compound (1) (395 mg) was dissolved in acetone (4 ml) to prepare a solution. 4-Hydroxythiophenol (314 mg) and potassium carbonate (344 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(3-fluorophenoxy)ethyl]sulfanyl}phenol (2) (323 mg, yield 54%).

Chlorobenzene (0.4 ml) was added to the compound (2) (230 mg) and 4-chloro-6,7-dimethoxyquinoline (390 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (137 mg, yield 35%).

The resultant compound (110 mg) was dissolved in a 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 93 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.44 (t, J=6.3 Hz, 2H), 4.03 (s, 3H), 4.04 (s, 3H), 4.23 (t, J=6.1 Hz, 2H), 6.74-6.84 (m, 3H), 6.86 (d, J=6.6 Hz, 1H), 7.27-7.41 (m, 3H), 7.61-7.66 (m, 3H), 7.73 (s, 1H), 8.78 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 452 (M⁺+1)

Example 822 4-(4-{[2-(2-Fluorophenoxy)ethyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinoline

o-Fluorophenol (0.6 g) was dissolved in acetone (2 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.67 ml), potassium carbonate (1.11 g), and tetra-n-butylammonium iodide (198 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-chloroethoxy)-2-fluorobenzene (1) (406 mg, yield 44%).

The compound (1) (387 mg) was dissolved in acetone (2 ml) to prepare a solution. 4-Hydroxythiophenol (308 mg) and potassium carbonate (338 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(2-fluorophenoxy)ethyl]sulfanyl}phenol (2) (244 mg, yield 42%).

Chlorobenzene (0.4 ml) was added to the compound (2) (191 mg) and 4-chloro-6,7-dimethoxyquinoline (324 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (132 mg, yield 40%).

The resultant compound (106 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 105 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.48 (t, J=6.6 Hz, 2H), 4.04 (s, 3H), 4.05 (s, 3H), 4.29 (t, J=6.3 Hz, 2H), 6.89 (d, J=6.6 Hz, 1H), 6.93-7.00 (m, 1H), 7.09-7.25 (m, 3H), 7.37-7.43 (m, 2H), 7.62-7.69 (m, 3H), 7.75 (s, 1H), 8.82 (d, J=6.8 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 452 (M⁺+1)

Example 823 6,7-Dimethoxy-4-(4-{[2-(3-methylphenoxy)ethyl]sulfanyl}phenoxy)quinoline

m-Cresol (0.6 g) was dissolved in acetone (3 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.69 ml), potassium carbonate (1.15 g), and tetra-n-butylammonium iodide (205 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-chloroethoxy)-3-methylbenzene (1) (349 mg, yield 37%).

The compound (1) (337 mg) was dissolved in acetone (3 ml) to prepare a solution. 4-Hydroxythiophenol (275 mg) and potassium carbonate (301 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(3-methylphenoxy)ethyl]sulfanyl}phenol (2) (188 mg, yield 36%).

Chlorobenzene (0.3 ml) was added to the compound (2) (160 mg) and 4-chloro-6,7-dimethoxyquinoline (276 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (129 mg, yield 47%).

The resultant compound (102 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 68 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.27 (s, 3H), 3.43 (t, J=6.3 Hz, 2H), 4.02 (s, 3H), 4.04 (s, 3H), 4.19 (t, J=6.3 Hz, 2H), 6.69-6.78 (m, 3H), 6.84-6.88 (m, 1H), 7.16 (t, J=7.8 Hz, 1H), 7.36-7.41 (m, 2H), 7.59-7.65 (m, 3H), 7.72 (s, 1H), 8.78 (d, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 448 (M⁺+1)

Example 824 4-(4-{[2-(4-Fluorophenoxy)ethyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinoline

4-Fluorophenol (0.6 g) was dissolved in acetone (3 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.69 ml), potassium carbonate (1.11 g), and tetra-n-butylammonium iodide (198 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-chloroethoxy)-4-fluorobenzene (1) (352 mg, yield 38%).

The compound (1) (342 mg) was dissolved in acetone (4 ml) to prepare a solution. 4-Hydroxythiophenol (273 mg) and potassium carbonate (299 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(4-fluorophenoxy)ethyl]sulfanyl}phenol (2) (233 mg, yield 45%).

Chlorobenzene (0.4 ml) was added to the compound (2) (211 mg) and 4-chloro-6,7-dimethoxyquinoline (357 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (181 mg, yield 50%).

The resultant compound (106 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 101 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.43 (t, J=6.6 Hz, 2H), 4.03 (s, 3H), 4.05 (s, 3H), 4.19 (t, J=6.1 Hz, 2H), 6.88 (d, J=6.8 Hz, 1H), 6.92-6.97 (m, 2H), 7.08-7.14 (m, 2H), 7.37-7.42 (m, 2H), 7.60-7.68 (m, 3H), 7.74 (s, 1H), 8.81 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 452 (M⁺+1)

Example 825 4-(4-{2-(2,4-Dichlorophenoxy)ethyl]-sulfanyl phenoxy)-6,7-dimethoxyquinoline

2,4-Dichlorophenol (0.6 g) was dissolved in acetone (3 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.46 ml), potassium carbonate (763 mg), and tetra-n-butylammonium iodide (136 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 2,4-dichloro-1-(2-chloroethoxy)benzene (1) (475 mg, yield 57%).

The compound (1) (462 mg) was dissolved in acetone (4 ml) to prepare a solution. 4-Hydroxythiophenol (285 mg) and potassium carbonate (312 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(2,4-dichlorophenoxy)ethyl]sulfanyl}phenol (2) (342 mg, yield 53%).

Chlorobenzene (0.3 ml) was added to the compound (2) (230 mg) and 4-chloro-6,7-dimethoxyquinoline (326 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (185 mg, yield 51%).

The resultant compound (103 mg) was dissolved in a 10% hydrochloric acid-methanol solution (10 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 83 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.48 (t, J=6.8 Hz, 2H), 4.03 (s, 3H), 4.05 (s, 3H), 4.31 (t, J=6.1 Hz, 2H), 6.85-6.90 (m, 1H), 7.17-7.22 (m, 1H), 7.34-7.42 (m, 3H), 7.56-7.67 (m, 4H), 7.74 (s, 1H), 8.78-8.83 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 826 4-(4-{[2-(2,4-Dimethylphenoxy)ethyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinoline

2,4-Dimethylphenol (0.6 g) was dissolved in acetone (3 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.61 ml), potassium carbonate (1.02 g), and tetra-n-butylammonium iodide (183 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-chloroethoxy)-2,4-dimethylbenzene (1) (231 mg, yield 26%).

The compound (1) (224 mg) was dissolved in acetone (2 ml) to prepare a solution. 4-Hydroxythiophenol (168 mg) and potassium carbonate (184 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(2,4-dimethylphenoxy)ethyl]sulfanyl}phenol (2) (124 mg, yield 38%).

Chlorobenzene (0.3 ml) was added to the compound (2) (112 mg) and 4-chloro-6,7-dimethoxyquinoline (182 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (68 mg, yield 36%).

The resultant compound (51 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 35 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.08 (s, 3H), 2.18 (s, 3H), 3.40-3.45 (m, 2H), 4.01 (s, 3H), 4.03 (s, 3H), 4.16 (t, J=6.1 Hz, 2H), 6.75-6.95 (m, 4H), 7.33-7.40 (m, 2H), 7.56 (s, 1H), 7.57-7.64 (m, 2H), 7.71 (s, 1H), 8.77 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 462 (M⁺+1)

Example 827 4-(4-{[2-(3,4-Dimethylphenoxy)ethyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinoline

3,4-Dimethylphenol (0.6 g) was dissolved in acetone (3 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.61 ml), potassium carbonate (1.02 g), and tetra-n-butylammonium iodide (183 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-chloroethoxy)-3,4-dimethylbenzene (1) (286 mg, yield 32%).

The compound (1) (279 mg) was dissolved in acetone (2 ml) to prepare a solution. 4-Hydroxythiophenol (210 mg) and potassium carbonate (230 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(3,4-dimethylphenoxy)ethyl]sulfanyl}phenol (2) (190 mg, yield 46%).

Chlorobenzene (0.3 ml) was added to the compound (2) (138 mg) and 4-chloro-6,7-dimethoxyquinoline (226 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (122 mg, yield 52%).

The resultant compound (68 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 34 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.13 (s, 3H), 2.18 (s, 3H), 3.40 (t, J=6.3 Hz, 2H), 4.02 (s, 3H), 4.04 (s, 3H), 4.15 (t, J=6.3 Hz, 2H), 6.61-6.74 (m, 2H), 6.87 (d, J=6.6 Hz, 1H), 7.02 (d, J=8.1 Hz, 1H), 7.38 (d, J=8.8 Hz, 2H), 7.54-7.66 (m, 3H), 7.72 (s, 1H), 8.78 (d, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 462 (M⁺+1)

Example 828 4-(4-{[2-(2,6-Dimethylphenoxy)ethyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinoline

2,6-Dimethylphenol (1 g) was dissolved in acetone (4 ml) to prepare a solution. 1-Bromo-2-chloroethane (1.02 ml), potassium carbonate (1.70 g), and tetra-n-butylammonium iodide (303 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-chloroethoxy)-2,6-dimethylbenzene (1) (513 mg, yield 34%).

The compound (1) (513 mg) was dissolved in acetone (4 ml) to prepare a solution. 4-Hydroxythiophenol (386 mg) and potassium carbonate (423 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(2,6-dimethylphenoxy)ethyl]sulfanyl}phenol (2) (319 mg, yield 42%).

Chlorobenzene (0.5 ml) was added to the compound (2) (281 mg) and 4-chloro-6,7-dimethoxyquinoline (456 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (29 mg, yield 6%).

The resultant compound (29 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 25 mg of a hydrochloride.

¹H-NMR (chloroform-d, 400 MHz): δ 2.29 (s, 3H), 2.34 (s, 3H), 3.41 (s, 1H), 3.95-4.30 (m, 9H), 6.85-8.30 (m, 11H)

Mass spectrometry value (ESI-MS, m/z): 462 (M⁺+1)

Example 829 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl [2-(4-fluorophenoxy)ethyl]sulfone

4-(4-{[2-(4-Fluorophenoxy)ethyl]sulfanyl}phenoxy)-6,7-dimethoxyquinoline (20 mg) was dissolved in acetic acid (0.5 ml) to prepare a solution. Potassium permanganate (35 mg) was added to the solution, and the mixture was stirred at room temperature for 2 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (16 mg, yield 76%).

The resultant compound (16 mg) was dissolved in a 10% hydrochloric acid-methanol solution (2 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 17 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.91 (t, J=5.6 Hz, 2H), 3.99 (s, 3H), 4.03 (s, 3H), 4.30 (t, J=5.4 Hz, 2H), 6.74-6.81 (m, 2H), 6.92 (d, J=6.3 Hz, 1H), 7.04-7.13 (m, 2H), 7.57 (s, 1H), 7.59-7.66 (m, 2H), 7.68 (s, 1H), 8.06-8.13 (m, 2H), 8.81 (d, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 484 (M⁺+1)

Example 830 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl [2-(3-methoxyphenoxy)ethyl]sulfone

6,7-Dimethoxy-4-(4-{[2-3-methoxyphenoxy)ethyl]-sulfanyl}phenoxy)quinoline (20 mg) was dissolved in acetic acid (0.5 ml) to prepare a solution. Potassium permanganate (34 mg) was added to the solution, and the mixture was stirred at room temperature for 2 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (9 mg, yield 40%).

The resultant compound (9 mg) was dissolved in a 10% hydrochloric acid-methanol solution (2 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 9 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.70 (s, 3H), 3.91 (t, J=5.6 Hz, 2H), 4.01 (s, 3H), 4.04 (s, 3H), 4.31 (t, J=5.6 Hz, 2H), 6.23 (t, J=2.4 Hz, 1H), 6.32-6.37 (m, 1H), 6.50-6.55 (m, 1H), 6.93 (d, J=6.1 Hz, 1H), 7.16 (t, J=8.3 Hz, 1H), 7.57-7.69 (m, 4H), 8.07-8.13 (m, 2H), 8.80 (d, J=6.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 831 2-(2,4-Dichlorophenoxy)ethyl{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}sulfone

4-(4-{[2-(2,4-Dichlorophenoxy)ethyl]sulfanyl}-phenoxy)-6,7-dimethoxyquinoline (20 mg) was dissolved in acetic acid (0.5 ml) to prepare a solution. Potassium permanganate (32 mg) was added to the solution, and the mixture was stirred at room temperature for 2 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (15 mg, yield 69%).

The resultant compound (15 mg) was dissolved in a 10% hydrochloric acid-methanol solution (2 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 15 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.94-4.07 (m, 8H), 4.42 (t, J=5.4 Hz, 2H), 6.91 (d, J=6.3 Hz, 1H), 7.19 (d, J=9.0 Hz, 1H), 7.33-7.37 (m, 1H), 7.52-7.67 (m, 5H), 7.97-8.03 (m, 2H), 8.80 (d, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 533 (M⁺+1)

Example 832 2-(3-Chlorophenoxy)ethyl{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}sulfone

4-(4-{[2-(3-Chlorophenoxy)ethyl]sulfanyl}phenoxy)-6,7-dimethoxyquinoline (20 mg) was dissolved in acetic acid (0.5 ml) to prepare a solution. Potassium permanganate (31 mg) was added to the solution, and the mixture was stirred at room temperature for 2 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (10 mg, yield 50%).

The resultant compound (10 mg) was dissolved in a 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 10 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.92 (t, J=5.4 Hz, 2H), 3.99 (s, 3H), 4.03 (s, 3H), 4.35 (t, J=5.6 Hz, 2H), 6.70-6.76 (m, 1H), 6.78 (t, J=2.0 Hz, 1H), 6.94 (d, J=6.3 Hz, 1H), 6.97-7.03 (m, 1H), 7.28 (t, J=8.3 Hz, 1H), 7.58 (s, 1H), 7.60-7.67 (m, 2H), 7.68 (s, 1H), 8.06-8.13 (m, 2H), 8.81 (d, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 500 (M⁺+1)

Example 833 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl [2-(3,4-dimethylphenoxy)ethyl]sulfone

4-(4-{[2-(3,4-Dimethylphenoxy)ethyl]sulfanyl}-phenoxy)-6,7-dimethoxyquinoline (19 mg) was dissolved in acetic acid (0.5 ml) to prepare a solution. Potassium permanganate (33 mg) was added to the solution, and the mixture was stirred at room temperature for 2 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (4 mg, yield 17%).

The resultant compound (4 mg) was dissolved in a 10% hydrochloric acid-methanol solution (2 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 4 mg of a hydrochloride.

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 834 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl [2-(4-methylphenoxy)ethyl]sulfone

6,7-Dimethoxy-4-(4-{[2-(4-methylphenoxy)ethyl]-sulfanyl}phenoxy)quinoline (20 mg) was dissolved in acetic acid (0.5 ml) to prepare a solution. Potassium permanganate (32 mg) was added to the solution, and the mixture was stirred at room temperature for 3 hr. Thereafter, water was further added thereto, and the mixture was stirred at room temperature for 5 min. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (1 mg, yield 4%).

The resultant compound (1 mg) was dissolved in a 10% hydrochloric acid-methanol solution (2 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 1 mg of a hydrochloride.

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 835 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl [2-(4-isopropylphenoxy)ethyl]sulfone

4-(4-{[2-(4-Isopropylphenoxy)ethyl]sulfanyl}-phenoxy)-6,7-dimethoxyquinoline (22 mg) was dissolved in acetic acid (0.5 ml) to prepare a solution. Potassium permanganate (34 mg) was added to the solution, and the mixture was stirred at room temperature for 3 hr. Thereafter, water was further added thereto, and the mixture was stirred at room temperature for 10 min. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (2 mg, yield 8%).

The resultant compound (2 mg) was dissolved in a 10% hydrochloric acid-methanol solution (2 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 2 mg of a hydrochloride.

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 836 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl [2-(2-isopropylphenoxy)ethyl]sulfone

4-(4-{[2-(2-Isopropylphenoxy)ethyl]sulfanyl}-phenoxy)-6,7-dimethoxyquinoline (12 mg) was dissolved in acetic acid (0.5 ml) to prepare a solution. Potassium permanganate (19 mg) was added to the solution, and the mixture was stirred at room temperature for 2 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (7 mg, yield 57%).

The resultant compound (7 mg) was dissolved in a 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 7 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.04 (s, 3H), 1.06 (s, 3H), 2.70-2.80 (m, 1H), 3.91-4.06 (m, 8H), 4.32 (t, J=5.4 Hz, 2H), 6.87-6.98 (m, 3H), 7.09-7.18 (m, 2H), 7.54-7.66 (m, 4H), 8.09-8.17 (m, 2H), 8.78 (d, J=6.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 837 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl [2-(2-fluorophenoxy)ethyl]sulfone

4-(4-{[2-(2-Fluorophenoxy)ethyl]sulfanyl}-phenoxy)-6,7-dimethoxyquinoline (20 mg) was dissolved in acetic acid (0.5 ml) to prepare a solution. Potassium permanganate (33 mg) was added to the solution, and the mixture was stirred at room temperature for 2 hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (7 mg, yield 37%).

The resultant compound (7 mg) was dissolved in a 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 7 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93-4.04 (m, 8H), 4.41 (t, J=5.4 Hz, 2H), 6.87-7.23 (m, 5H), 7.56-7.64 (m, 3H), 7.67 (s, 1H), 8.11 (d, J=8.5 Hz, 2H), 8.84 (d, J=6.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 484 (M⁺+1)

Example 838 {4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}[2-(3-methoxy-4-nitrophenoxy)ethyl]sulfoxide

Nitric acid (0.5 ml) was added to 6,7-dimethoxy-4-(4-{[2-(3-methoxyphenoxy)ethyl]sulfanyl}phenoxy)-quinoline (20 mg), and the mixture was stirred at 0° C. for 30 min. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (14 mg, yield 60%).

The resultant compound (14 mg) was dissolved in a 10% hydrochloric acid-methanol solution (2 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 15 mg of a hydrochloride.

Mass spectrometry value (ESI-MS, m/z): 541 (M⁺+1)

Example 839 {4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}[2-(4-fluoro-2-nitrophenoxy)ethyl]sulfoxide

Nitric acid (0.5 ml) was added to 4-(4-{[2-(4-Fluorophenoxy)ethyl]sulfanyl}phenoxy)-6,7-dimethoxyquinoline (20 mg), and the mixture was stirred at 0° C. for 30 min. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (13 mg, yield 58%).

The resultant compound (13 mg) was dissolved in a 10% hydrochloric acid-methanol solution (2 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 14 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.50-3.58 (m, 2H), 4.03 (s, 3H), 4.05 (s, 3H), 4.53 (t, J=4.9 Hz, 2H), 6.93-6.97 (m, 1H), 7.47-7.65 (m, 5H), 7.73 (s, 1H), 7.87-7.94 (m, 3H), 8.80 (d, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 513 (M⁺+1)

Example 840 [2-(2,4-Dichlorophenoxy)ethyl]{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}sulfoxide

Nitric acid (0.5 ml) was added to 4-(4-{[2-(2,4-dichlorophenoxy)ethyl]sulfanyl}phenoxy)-6,7-dimethoxyquinoline (20 mg), and the mixture was stirred at 0° C. for one hr. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography using chloroform/methanol for development to give the title compound (19 mg, yield 92%).

The resultant compound (19 mg) was dissolved in a 10% hydrochloric acid-methanol solution (2 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 19 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.50-3.62 (m, 2H), 4.02 (s, 3H), 4.05 (s, 3H), 4.39-4.49 (m, 2H), 6.91 (d, J=6.3 Hz, 1H), 7.26 (d, J=9.0 Hz, 1H), 7.37-7.43 (m, 1H), 7.57-7.64 (m, 4H), 7.72 (s, 1H), 7.90-7.97 (m, 2H), 8.81 (d, J=6.3 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 518 (M⁺+1)

Example 841 6,7-Dimethoxy-4-(4-{[3-(3-methylphenoxy)propyl]sulfanyl}phenoxy)quinoline

m-Cresol (0.6 g) was dissolved in acetonitrile (2 ml) to prepare a solution. 1,3-Dibromopropane (1.13 ml), potassium carbonate (2.30 g), and tetra-n-butylammonium iodide (205 mg) were then added to the solution, and the mixture was heated under reflux for 3 hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropoxy)-3-methylbenzene (1) (831 mg, yield 65%).

The compound (1) (1.07 g) was dissolved in acetone (5 ml) to prepare a solution. 4-Hydroxythiophenol (647 mg) and potassium carbonate (709 mg) were then added to the solution, and the mixture was stirred at room temperature for 2 hr. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[3-(3-methylphenoxy)propyl]sulfanyl}phenol (2) (1.00 g, yield 78%).

Chlorobenzene (0.4 ml) was added to the compound (2) (200 mg) and 4-chloro-6,7-dimethoxyquinoline (326 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (134 mg, yield 37%).

The resultant compound (110 mg) was dissolved in a 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 103 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.05 (t, J=6.8 Hz, 2H), 2.27 (s, 3H), 3.19 (t, J=7.3 Hz, 2H), 4.04 (s, 3H), 4.05 (s, 3H), 4.08 (t, J=6.1 Hz, 2H), 6.70-6.77 (m, 3H), 6.88 (d, J=6.6 Hz, 1H), 7.16 (t, J=8.3 Hz, 1H), 7.37-7.42 (m, 2H), 7.55-7.61 (m, 2H), 7.69 (s, 1H), 7.75 (s, 1H), 8.80 (d, J=6.6 Hz, 1H)

Example 842 4-(4-{[3-(2-Fluorophenoxy)propyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinoline

o-Fluorophenol (0.6 g) was dissolved in acetonitrile (2 ml) to prepare a solution. 1,3-Dibromopropane (1.09 ml), potassium carbonate (2.22 g), and tetra-n-butylammonium iodide (198 mg) were then added to the solution, and the mixture was heated under reflux for one hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropoxy)-3-methylbenzene (1) (930 mg, yield 75%).

The compound (1) (1.10 g) was dissolved in acetone (5 ml) to prepare a solution. 4-Hydroxythiophenol (657 mg) and potassium carbonate (720 mg) were then added to the solution, and the mixture was stirred at room temperature for 2 hr. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[3-(2-fluorophenoxy)propyl]sulfanyl}phenol (2) (853 mg, yield 65%).

Chlorobenzene (0.4 ml) was added to the compound (2) (200 mg) and 4-chloro-6,7-dimethoxyquinoline (322 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (167 mg, yield 50%).

The resultant compound (139 mg) was dissolved in a 10% hydrochloric acid-methanol solution (8 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 132 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.04-2.13 (m, 2H), 3.20 (t, J=7.1 Hz, 2H), 4.04 (s, 3H), 4.05 (s, 3H), 4.18 (t, J=6.1 Hz, 2H), 6.87 (d, J=6.6 Hz, 1H), 6.91-6.98 (m, 1H), 7.10-7.24 (m, 3H), 7.36-7.42 (m, 2H), 7.59-7.63 (m, 2H), 7.69 (s, 1H), 7.74 (s, 1H), 8.80 (d, J=6.6 Hz, 1H)

Example 843 4-(4-{[4-(2-Fluorophenoxy)butyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinoline

o-Fluorophenol (1.0 g) was dissolved in acetonitrile (3 ml) to prepare a solution. 1,4′-Dibromobutane (2.13 ml), potassium carbonate (3.70 g), and tetra-n-butylammonium iodide (330 mg) were then added to the solution, and the mixture was heated under reflux for one hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(4-bromobutoxy)-2-fluorobenzene (1) (1.57 g, yield 71%).

The compound (1) (1.55 g) was dissolved in acetone (4 ml) to prepare a solution. 4-Hydroxythiophenol (873 mg) and potassium carbonate (956 mg) were then added to the solution, and the mixture was stirred at room temperature for 2 hr. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[4-(2-fluorophenoxy)butyl]sulfanyl}phenol (2) (1.66 g, yield 90%).

Chlorobenzene (0.4 ml) was added to the compound (2) (200 mg) and 4-chloro-6,7-dimethoxyquinoline (306 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (156 mg, yield 47%).

The resultant compound (99 mg) was dissolved in a 10% hydrochloric acid-methanol solution (4 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 69 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.73-1.95 (m, 4H), 3.12 (t, J=7.3 Hz, 2H), 4.03 (s, 3H), 4.04 (s, 3H), 4.09 (t, J=6.1 Hz, 2H), 6.86 (d, J=6.6 Hz, 1H), 6.88-6.97 (m, 1H), 7.08-7.23 (m, 3H), 7.34-7.39 (m, 2H), 7.52-7.57 (m, 2H), 7.61 (s, 1H), 7.73 (s, 1H), 8.78 (d, J=6.3 Hz, 1H)

Example 844 6,7-Dimethoxy-4-(4-{[4-(3-methylphenoxy)butyl]sulfanyl}phenoxy)quinoline

m-Cresol (1 g) was dissolved in acetonitrile (3 ml) to prepare a solution. 1,4-Dibromobutane (2.21 ml), potassium carbonate (3.84 g), and tetra-n-butylammonium iodide (342 mg) were then added to the solution, and the mixture was heated under reflux for one hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(4-bromobutoxy)-3-methylbenzene (1).

The compound (1) was dissolved in acetone (4 ml) to prepare a solution. 4-Hydroxythiophenol (2.07 g) and potassium carbonate (2.27 g) were then added to the solution, and the mixture was stirred at room temperature for 6 hr. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[4-(3-methylphenoxy)butyl]sulfanyl}phenol (2) (1.04 g, yield 39%).

Chlorobenzene (0.4 ml) was added to the compound (2) (200 mg) and 4-chloro-6,7-dimethoxyquinoline (309 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (139 mg, yield 42%).

The resultant compound (115 mg) was dissolved in a 10% hydrochloric acid-methanol solution (6 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 85 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.72-1.91 (m, 4H), 2.26 (s, 3H), 3.11 (t, J=7.1 Hz, 2H), 3.98 (t, J=6.3 Hz, 2H), 4.03 (s, 3H), 4.04 (s, 3H), 6.68-6.76 (m, 3H), 6.86 (d, J=6.6 Hz, 1H), 7.11-7.17 (m, 1H), 7.33-7.39 (m, 2H), 7.52-7.57 (m, 2H), 7.60 (s, 1H), 7.73 (s, 1H), 8.78 (d, J=6.6 Hz, 1H)

Example 845 4-(4-{[3-(2-Fluorophenoxy)propyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinazoline

o-Fluorophenol (0.6 g) was dissolved in acetonitrile (2 ml) to prepare a solution. 1,3-Dibromopropane (1.09 ml), potassium carbonate (2.22 g), and tetra-n-butylammonium iodide (198 mg) were then added to the solution, and the mixture was heated under reflux for one hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropoxy)-2-fluorobenzene (1) (930 mg, yield 75%).

The compound (1) (1.10 g) was dissolved in acetone (5 ml) to prepare a solution. 4′-Hydroxythiophenol (657 mg) and potassium carbonate (720 mg) were then added to the solution, and the mixture was stirred at room temperature for 2 hr. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[3-(2-fluorophenoxy)propyl]sulfanyl}phenol (2) (0.85 g, yield 65%).

Chlorobenzene (0.3 ml) was added to the compound (2) (100 mg) and 4-chloro-6,7-dimethoxyquinazoline (163 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (65 mg, yield 39%).

The resultant compound (60 mg) was dissolved in a 10% hydrochloric acid-methanol solution (8 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 36 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.01-2.10 (m, 2H), 3.16 (t, J=7.3 Hz, 2H), 3.99 (s, 3H), 4.00 (s, 3H), 4.13-4.23 (m, 2H), 6.90-6.93 (m, 1H), 7.09-7.51 (m, 8H), 7.58 (s, 1H), 8.65 (s, 1H)

Example 846 6,7-Dimethoxy-4-(4-{[3-(3-methylphenoxy)propyl]sulfanyl}phenoxy)quinazoline

m-Cresol (0.6 g) was dissolved in acetonitrile (2 ml) to prepare a solution. 1,3-Dibromopropane (1.13 ml), potassium carbonate (2.30 g), and tetra-n-butylammonium iodide (205 mg) were then added to the solution, and the mixture was heated under reflux for 3 hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(3-bromopropoxy)-3-methylbenzene (1) (831 mg, yield 65%).

The compound (1) (1.07 g) was dissolved in acetone (5 ml) to prepare a solution. 4-Hydroxythiophenol (647 mg), potassium carbonate (709 mg) were then added to the solution, and the mixture was stirred at room temperature for 2 hr. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[3-(3-methylphenoxy)propyl]sulfanyl}phenol (2) (1.00 g, yield 78%).

Chlorobenzene (0.3 ml) was added to the compound (2) (100 mg) and 4-chloro-6,7-dimethoxyquinazoline (165 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (82 mg, yield 49%).

The resultant compound (70 mg) was dissolved in a 10% hydrochloric acid-methanol solution (3 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 12 mg of a hydrochloride.

Mass spectrometry value (ESI-MS, m/z): 463 (M⁺+1)

Example 847 6,7-Dimethoxy-4-(4-{[4-(3-methylphenoxy)butyl]sulfanyl}phenoxy)quinazoline

m-Cresol (1 g) was dissolved in acetonitrile (3 ml) to prepare a solution. 1,4-Dibromobutane (2.21 ml), potassium carbonate (3.84 g), and tetra-n-butylammonium iodide (342 mg) were then added to the solution, and the mixture was heated under reflux for one hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(4-bromobutoxy)-3-methylbenzene (1).

The compound (1) was dissolved in acetone (4 ml) to prepare a solution. 4-Hydroxythiophenol (2.07 g) and potassium carbonate (2.27 g) were then added to the solution, and the mixture was stirred at room temperature for 6 hr. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[4-(3-methylphenoxy)butyl]-sulfanyl}phenol (2) (1.04 g, yield 39%).

Chlorobenzene (0.4 ml) was added to the compound (2) (100 mg) and 4-chloro-6,7-dimethoxyquinazoline (156 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (110 mg, yield 66%).

The resultant compound (95 mg) was dissolved in a 10% hydrochloric acid-methanol solution (8 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 60 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.71-1.91 (m, 4H), 2.26 (s, 3H), 3.07 (t, J=7.1 Hz, 2H), 3.93-4.04 (m, 8H), 6.68-6.76 (m, 3H), 7.14 (t, J=8.1 Hz, 1H), 7.25-7.31 (m, 2H), 7.38-7.48 (m, 3H), 7.59 (s, 1H), 8.64 (s, 1H)

Example 848 4-(4-{[4-(2-Fluorophenoxy)butyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinazoline

o-Fluorophenol (1.0 g) was dissolved in acetonitrile (3 ml) to prepare a solution. 1,4-Dibromobutane (2.13 ml), potassium carbonate (3.70 g), and tetra-n-butylammonium iodide (330 mg) were then added to the solution, and the mixture was heated under reflux for one hr. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(4-bromobutoxy)-2-fluorobenzene (1) (1.57 g, yield 71%).

The compound (1) (1.55 g) was dissolved in acetone (4 ml) to prepare a solution. 4-Hydroxythiophenol (873 mg) and potassium carbonate (956 mg) were then added to the solution, and the mixture was stirred at room temperature for 2 hr. 1 N HCl was added to reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[3-(2-fluorophenoxy)butyl]sulfanyl}phenol (2) (1.66 g, yield 90%).

Chlorobenzene (0.4 ml) was added to the compound (2) (100 mg) and 4-chloro-6,7-dimethoxyquinazoline (154 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (117 mg, yield 73%).

The resultant compound (96 mg) was dissolved in a 10% hydrochloric acid-methanol solution (6 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Ethyl acetate was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 81 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.73-1.94 (m, 4H), 3.09 (t, J=7.3 Hz, 2H), 3.99 (s, 3H), 4.01 (s, 3H), 4.08 (t, J=6.3 Hz, 2H), 6.87-6.96 (m, 1H), 7.07-7.22 (m, 3H), 7.27-7.32 (m, 2H), 7.43-7.48 (m, 3H), 7.61 (s, 1H), 8.71 (s, 1H)

Example 849 4-(4-{[2-(2-Fluorophenoxy)ethyl]-sulfanyl}phenoxy)-6,7-dimethoxyquinazoline

o-Fluorophenol (0.6 g) was dissolved in acetone (2 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.69 ml), potassium carbonate (1.11 g), and tetra-n-butylammonium iodide (198 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-chloroethoxy)-2-fluorobenzene (1) (438 mg, yield 47%).

The compound (1) (432 mg) was dissolved in acetone (3 ml) to prepare a solution. 4-Hydroxythiophenol (343 mg) and potassium carbonate (376 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(2-fluorophenoxy)ethyl]sulfanyl}phenol (2) (345 mg, yield 53%).

Chlorobenzene (0.4 ml) was added to the compound (2) (100 mg) and 4-chloro-6,7-dimethoxyquinazoline (171 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (110 mg, yield 64%).

The resultant compound (90 mg) was dissolved in a 10% hydrochloric acid-methanol solution (6 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 60 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.42 (t, J=6.6 Hz, 2H), 3.98 (s, 3H), 4.00 (s, 3H), 4.26 (t, J=6.3 Hz, 2H), 6.92-6.99 (m, 1H), 7.08-7.62 (m, 9H), 8.65 (s, 1H)

Example 850 6,7-Dimethoxy-4-(4-{[2-(3-methylphenoxy)ethyl]sulfanyl}phenoxy)quinazoline

m-Cresol (0.6 g) was dissolved in acetone (2 ml) to prepare a solution. 1-Bromo-2-chloroethane (0.69 ml), potassium carbonate (1.15 g), and tetra-n-butylammonium iodide (205 mg) were then added to the solution, and the mixture was heated under reflux overnight. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using hexane/ethyl acetate for development to give 1-(2-chloroethoxy)-3-methylbenzene (1) (347 mg, yield 37%).

The compound (1) (341 mg) was dissolved in acetone (3 ml) to prepare a solution. 4-Hydroxythiophenol (278 mg) and potassium carbonate (304 mg) were then added to the solution, and the mixture was stirred at room temperature overnight. 1 N HCl was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using chloroform for development to give 4-{[2-(3-methylphenoxy)ethyl]sulfanyl}phenol (2) (243 mg, yield 47%).

Chlorobenzene (0.4 ml) was added to the compound (2) (100 mg) and 4-chloro-6,7-dimethoxyquinazoline (174 mg), and the mixture was stirred at 140° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform, followed by washing with saturated brine. The extract was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel using hexane/acetone for development to give the title compound (86 mg, yield 50%).

The resultant compound (72 mg) was dissolved in a 10% hydrochloric acid-methanol solution (6 ml) to prepare a solution which was then allowed to stand at room temperature for 10 min. The solvent was removed by distillation under the reduced pressure. Diethyl ether was then added to the residue, and the precipitated crystal was collected by filtration and was washed to give 52 mg of a hydrochloride.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.27 (s, 3H), 3.38 (t, J=6.3 Hz, 2H), 3.98 (s, 3H), 4.00 (s, 3H), 4.17 (t, J=6.3 Hz, 2H), 6.68-6.78 (m, 3H), 7.12-7.18 (m, 1H), 7.27-7.34 (m, 2H), 7.41 (s, 1H), 7.50-7.56 (m, 2H), 7.58 (s, 1H), 8.62 (s, 1H)

Example 851 N-[2-(2,4-Dichlorophenoxy)ethyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}amine

Sodium hydride (60 mg) was dissolved in dimethylformamide (3 ml) to prepare a solution. A dimethylformamide solution (5 ml) of 2,4-dichlorophenol (245 mg) was then added to the solution, and the mixture was stirred at room temperature for 10 min. Subsequently, a dimethylformamide solution (5 ml) of bromomethylacetate (344 mg) was added thereto, and the mixture was further stirred at room temperature for 90 min. Water was added to stop the reaction, and the reaction solution was extracted with ethyl acetate, followed by washing with water and saturated brine. The extract was then dried over sodium sulfate. After the concentration of the extract, a 5% aqueous sodium hydroxide solution (10 ml) was added thereto, and the mixture was stirred at 80° C. for 10 hr. Subsequently, the solution was acidified by the addition of 1 N hydrochloric acid. The resultant white precipitate was collected by filtration and was dried to give 2-(2,4-dichlorophenoxy)acetic acid (310 mg, yield 94%).

2-(2,4-Dichlorophenoxy)acetic acid (310 mg) was added to chloroform (5 ml), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (403 mg), 1-hydroxybenzotriazole monohydrate (284 mg), and 4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (498 mg) were added thereto. The mixture was then stirred with heating under reflux for 2 hr. A saturated aqueous sodium hydrogencarbonate solution was added to stop the reaction, and the reaction solution was extracted with chloroform, followed by washing with a saturated aqueous sodium hydrogencarbonate solution, 1 N hydrochloric acid, water, and saturated brine. The extract was then dried over sodium sulfate. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give N1-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-2-(2,4-dichlorophenoxy)acetamide (500 mg, yield 72%).

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(2,4-dichlorophenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (156 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.76 (t, J=5.4 Hz, 2H), 4.11 (s, 3H), 4.14 (s, 3H), 4.47 (t, J=5.4 Hz, 2H), 6.81 (d, J=6.6 Hz, 1H), 7.08 (d, J=8.8 Hz, 1H), 7.23-7.27 (m, 3H), 7.38 (d, J=2.7 Hz, 1H), 7.54 (d, J=8.8 Hz, 2H), 7.69-7.70 (m, 1H), 8.01 (s, 1H), 8.65 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 486 (M⁺+1)

Example 852 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-[2-(2-methylphenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(2-methylphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.11 (s, 3H), 3.88 (brs, 2H), 4.06 (s, 3H), 4.10 (s, 3H), 4.40 (brs, 2H), 6.72-6.76 (m, 3H), 6.96-7.01 (m, 2H), 7.28-7.32 (m, 2H), 7.53 (s, 1H), 7.88 (s, 1H), 7.96 (brs, 2H), 8.72 (brs, 1H)

Mass spectrometry value (ESI-MS, m/z): 431 (M⁺+1)

Example 853 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-[2-(2-methoxyphenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(2-methoxyphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 447 (M⁺+1)

Example 854 N-[2-(2,6-Dichlorophenoxy)ethyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(2,6-dichlorophenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (156 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.59 (brs, 2H), 4.04 (s, 3H), 4.05 (s, 3H), 4.29 (t, J=5.4 Hz, 2H), 4.54 (brs, 1H), 6.43 (d, J=5.4 Hz, 1H), 6.76 (d, J=9.0 Hz, 2H), 6.98-7.05 (m, 3H), 7.27-7.31 (m, 3H), 7.41 (s, 1H), 7.59 (s, 1H), 8.46 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 486 (M⁺+1)

Example 855 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-[2-(2,6-dimethylphenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(2,6-dimethylphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.29 (s, 6H), 3.55-3.56 (m, 2H), 3.99-4.02 (m, 2H), 4.03 (s, 3H), 4.04 (s, 3H), 4.38 (brs, 1H), 6.42 (d, J=5.4 Hz, 1H), 6.76 (d, J=8.8 Hz, 2H), 6.92-7.05 (m, 5H), 7.42 (s, 1H), 7.60 (s, 1H), 8.46 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 856 N-[2-(2,6-Dimethoxyphenoxy)ethyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(2,6-dimethoxyphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.37-3.39 (m, 2H), 3.85 (s, 3H), 3.88 (s, 3H), 4.039 (s, 3H), 4.044 (s, 3H), 4.28 (t, J=5.1 Hz, 2H), 5.01 (brs, 1H), 6.43 (d, J=5.4 Hz, 1H), 6.57-6.61 (m, 2H), 6.72 (d, J=8.8 Hz, 1H), 7.00-7.04 (m, 3H), 7.41 (s, 1H), 7.60 (s, 1H), 8.45 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 477 (M⁺+1)

Example 857 N-[2-(2,6-Difluorophenoxy)ethyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(2,6-difluorophenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 453 (M⁺+1)

Example 858 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-[2-(3,5-dimethylphenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(3,5-dimethylphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 859 N-[2-(4-Chlorophenoxy)ethyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}amine

N1-(4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(4-chlorophenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 452 (M⁺+1)

Example 860 N-[2-(3-Chlorophenoxy)ethyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(3-chlorophenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 452 (M⁺+1)

Example 861 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-[2-(2-ethylphenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(2-ethylphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 862 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N-[2-(2-methylphenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenyl}-2-(2-methylphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.26 (s, 3H), 3.58 (t, J=5.1 Hz, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 4.21 (t, J=5.4 Hz, 3H), 6.75-6.91 (m, 4H), 7.08-7.18 (m, 4H), 7.31 (s, 1H), 7.57 (s, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 432 (M⁺+1)

Example 863 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-[2-(4-methoxyphenoxy)ethyl]amine

N1-(4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(4-methoxyphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.52 (t, J=4.9 Hz, 2H), 3.77 (s, 3H), 4.04 (s, 3H), 4.05 (s, 3H), 4.15 (t, J=5.1 Hz, 2H), 6.74 (d, J=8.8 Hz, 2H), 6.83-6.89 (m, 4H), 7.03 (d, J=8.8 Hz, 2H), 7.41 (s, 1H), 7.59 (s, 1H), 8.45 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 447 (M⁺+1)

Example 864 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-[2-(4-ethylphenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(4-ethylphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 865 N-[2-(2,5-Dichlorophenoxy)ethyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(2,5-dichlorophenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 486 (M⁺+1)

Example 866 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-[2-(4-fluorophenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(4-fluorophenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 4.03 (s, 3H), 4.04 (s, 3H), 4.14 (t, J=5.4 Hz, 2H), 6.82-6.84 (m, 3H), 6.97-7.01 (m, 2H), 7.11-7.16 (m, 4H), 7.62 (s, 1H), 7.74 (s, 1H), 8.78 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 435 (M⁺+1)

Example 867 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-[2-(4-fluorophenoxy)ethyl]-N-methylamine

Dimethylformamide (240 ml) was added to sodium hydride (1.96 g), and N1-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl-2-(4-fluorophenoxy)acetamide (11 g) was added thereto. Subsequently, a dimethylformamide solution (10 ml) of methyl iodide (7 g) was added thereto, and the mixture was stirred at room temperature for 2 hr. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was then dried over sodium sulfate and was then concentrated, and the residue was purified on a column using hexane/acetone to give N1-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl-N1-methyl-2-(4-fluorophenoxy)acetamide (7.1 g, yield 63%).

N1-4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl-N1-methyl-2-(4-fluorophenoxy)acetamide (7.1 g) was dissolved in tetrahydrofuran (250 ml) to prepare a solution. A 1 M solution (46 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (3.2 g, yield 40%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.10 (s, 3H), 3.78 (t, J=5.9 Hz, 2H), 4.07 (s, 3H), 4.08 (s, 3H), 4.14 (t, J=5.9 Hz, 2H), 6.51 (d, J=5.6 Hz, 1H), 6.82-6.85 (m, 4H), 6.94-7.00 (m, 2H), 7.06-7.08 (m, 2H), 7.61 (s, 1H), 7.64 (s, 1H), 8.45 (d, J=5.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 449 (M⁺+1)

Example 868 N-[2-(2-Chlorophenoxy)ethyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(2-chlorophenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 452 (M⁺+1)

Example 869 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-(2-phenoxyethyl)amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-phenoxyacetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 417 (M⁺+1)

Example 870 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-[2-(4-methylphenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(4-methylphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 431 (M⁺+1)

Example 871 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-[2-(3-methylphenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(3-methylphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 431 (M⁺+1)

Example 872 2-(2-{4-[(6,7-Dimethoxy-4-quinolyl)-oxy]anilino}ethoxy)phenol

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(2-hydroxyphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 4.02 (s, 3H), 4.03 (s, 3H), 4.12 (t, J=5.4 Hz, 2H), 6.71-6.95 (m, 7H), 7.15-7.17 (m, 2H), 7.62 (s, 1H), 7.73 (s, 1H), 8.77 (d, J=6.6 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 433 (M⁺+1)

Example 873 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N-(2-phenoxyethyl)amine

N1-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenyl}-2-phenoxyacetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.56 (t, J=5.1 Hz, 2H), 4.07 (s, 6H), 4.21 (t, J=4.9 Hz, 2H), 6.76 (d, J=8.8 Hz, 2H), 6.93-7.00 (m, 3H), 7.09 (d, J=8.8 Hz, 2H), 7.28-7.33 (m, 2H), 7.39 (s, 1H), 7.57 (s, 1H), 8.65 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 418 (M⁺+1)

Example 874 2-(2-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilino}ethoxy)phenol

N1-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenyl}-2-(2-hydroxyphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 3.60 (t, J=5.4 Hz, 2H), 4.06 (s, 3H), 4.07 (s, 3H), 4.28 (t, J=5.4 Hz, 2H), 6.78 (d, J=8.8 Hz, 2H), 6.87-6.94 (m, 4H), 7.10 (d, J=9.0 Hz, 2H), 7.32 (s, 1H), 7.57 (s, 1H), 8.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 434 (M⁺+1)

Example 875 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-N-(2-phenoxyethyl)amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-2-phenoxyacetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 434 (M⁺+1)

Example 876 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-N-[2-(2-methylphenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-2-(2-methylphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.02 (s, 3H), 2.19 (s, 3H), 3.50 (t, J=4.9 Hz, 2H), 3.96 (s, 3H), 3.98 (s, 3H), 4.12 (t, J=4.9 Hz, 2H), 6.23 (d, J=5.1 Hz, 1H), 6.50-6.54 (m, 2H), 6.76-6.89 (m, 3H), 7.07-7.10 (m, 2H), 7.34 (s, 1H), 7.55 (s, 1H), 8.35-8.36 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 877 N-[2-(2-Chlorophenoxy)ethyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-methylphenyl}amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-2-(2-chlorophenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 3.60 (t, J=4.9 Hz, 2H), 4.04 (s, 3H), 4.06 (s, 3H), 4.26 (t, J=5.1 Hz, 2H), 6.31 (d, J=5.4 Hz, 1H), 6.59-6.65 (m, 2H), 6.91-6.97 (m, 3H), 7.20-7.22 (m, 1H), 7.38-7.40 (m, 1H), 7.42 (s, 1H), 7.63 (s, 1H), 8.43 (d, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 466 (M⁺+1)

Example 878 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-N-[2-(3-methylphenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-2-(3-methylphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 2.34 (s, 3H), 3.54 (t, J=4.9 Hz, 2H), 4.04 (s, 3H), 4.06 (s, 3H), 4.18 (t, J=5.1 Hz, 2H), 6.30 (d, J=5.4 Hz, 1H), 6.56-6.61 (m, 2H), 6.74-6.81 (m, 3H), 6.95 (d, J=8.3 Hz, 1H), 7.18 (t, J=7.6 Hz, 1H), 7.42 (s, 1H), 7.63 (s, 1H), 8.43 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 879 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-N-[2-(4-methylphenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-2-(4-methylphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): 2.10 (s, 3H), 2.30 (s, 3H), 3.53 (t, J=4.9 Hz, 2H), 4.04 (s, 3H), 4.06 (s, 3H), 4.17 (t, J=5.1 Hz, 2H), 6.30 (d, J=5.1 Hz, 1H), 6.56-6.61 (m, 2H), 6.83-6.96 (m, 3H), 7.10 (d, J=8.5 Hz, 2H), 7.42 (s, 1H), 7.63 (s, 1H), 8.43 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 880 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-N-[2-(2-methoxyphenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-2-(2-methoxyphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 3.55 (t, J=4.9 Hz, 2H), 3.89 (s, 3H), 4.04 (s, 3H), 4.06 (s, 3H), 4.25 (t, J=4.9 Hz, 2H), 6.29-6.31 (m, 1H), 6.57-6.61 (m, 1H), 6.89-7.11 (m, 6H), 7.43-7.44 (m, 1H), 7.61-7.65 (m, 1H), 8.44 (t, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 460 (M⁺+1)

Example 881 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-N-[2-(2,6-dimethylphenoxy)ethyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-2-(2,6-dimethylphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.11 (s, 3H), 2.30 (s, 6H), 3.55 (t, J=5.1 Hz, 2H), 4.02 (t, J=4.9 Hz, 2H), 4.05 (s, 3H), 4.07 (s, 3H), 6.30 (d, J=5.4 Hz, 1H), 6.60-6.64 (m, 2H), 6.94-6.98 (m, 2H), 7.02-7.04 (m, 2H), 7.43 (s, 1H), 7.63 (s, 1H), 8.44 (t, J=5.1 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 459 (M⁺+1)

Example 882 N-[2-(2,6-Dimethoxyphenoxy)ethyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-methylphenyl}amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-2-(2,6-dimethoxyphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (156 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 3.38 (brs, 2H), 3.89 (s, 6H), 4.05 (s, 3H), 4.06 (s, 3H), 4.27 (t, J=5.1 Hz, 2H), 4.94 (brs, 1H), 6.31 (d, J=5.1 Hz, 1H), 6.56-6.61 (m, 4H), 6.94 (d, J=8.5 Hz, 1H), 7.02 (t, J=8.3 Hz, 1H), 7.43 (s, 1H), 7.64 (s, 1H), 8.44 (t, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 491 (M⁺+1)

Example 883 N-[2-(2,6-Difluorophenoxy)ethyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-methylphenyl}amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-2-(2,6-difluorophenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 3.50 (brs, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 4.37 (t, J=5.1 Hz, 2H), 6.31 (d, J=5.4 Hz, 1H), 6.57-6.63 (m, 2H), 6.89-6.99 (m, 4H), 7.43 (s, 1H), 7.63 (s, 1H), 8.44 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 884 N-[2-(2,6-Dimethoxyphenoxy)ethyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-2-(2,6-dimethoxyphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (156 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.10 (s, 3H), 2.24 (s, 3H), 3.44 (t, J=4.4 Hz, 2H), 3.87 (s, 6H), 4.05 (s, 3H), 4.07 (s, 3H), 4.32 (t, J=4.6 Hz, 2H), 4.72 (brs, 1H), 6.27 (d, J=5.4 Hz, 1H), 6.58-6.62 (m, 3H), 6.91 (d, J=8.8 Hz, 1H), 7.03 (t, J=8.5 Hz, 1H), 7.43 (s, 1H), 7.66 (s, 1H), 8.42 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 505 (M⁺+1)

Example 885 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-(3-phenoxypropyl)amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-3-phenoxypropaneamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted With chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.30-2.33 (m, 2H), 3.91 (s, 3H), 3.98 (s, 3H), 4.00 (t, J=5.6 Hz, 2H), 4.34 (t, J=7.1 Hz, 2H), 6.21 (d, J=7.6 Hz, 1H), 6.86-7.01 (m, 7H), 7.27-7.32 (m, 3H), 7.47 (d, J=7.6 Hz, 1H), 7.83 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 431 (M⁺+1)

Example 886 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N-(3-phenoxypropyl)amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-3-phenoxypropaneamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 8.0%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.08 (s, 3H), 2.14 (s, 3H), 2.17-2.23 (m, 2H), 3.43 (t, J=6.3 Hz, 2H), 4.04 (s, 3H), 4.06 (s, 3H), 4.16 (t, J=5.9 Hz, 2H), 6.29 (d, J=5.4 Hz, 1H), 6.54 (s, 1H), 6.82 (s, 1H), 6.93-6.97 (m, 3H), 7.28-7.32 (m, 2H), 7.43 (s, 1H), 7.62 (s, 1H), 8.42 (d, J=5.4 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 459 (M⁺+1)

Example 887 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N-(3-phenoxypropyl)amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-3-phenoxypropaneamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mxitue was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solutions and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

¹H-NMR (CDCl₃-d₁, 400 MHz): δ 2.07 (s, 3H), 2.14 (s, 3H), 2.17-2.30 (m, 2H), 3.42 (t, J=6.3 Hz, 2H), 4.05 (s, 3H), 4.06 (s, 3H), 4.17 (t, J=5.9 Hz, 2H), 6.26 (d, J=5.4 Hz, 1H), 6.59 (d, J=8.5 Hz, 1H), 6.90-6.97 (m, 3H), 7.28-7.43 (m, 3H), 7.65 (s, 1H), 8.41 (d, J=5.4 Hz, 1H), 8.58 (d, J=4.9 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 459 (M⁺+1)

Example 888 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-[3-(2-methylphenoxy)propyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-3-(2-methylphenoxy)propaneamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 445 (M⁺+1)

Example 889 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N-[3-(2-methylphenoxy)propyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-3-(2-methylphenoxy)propaneamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 473 (M⁺+1)

Example 890 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N-[3-(2-methylphenoxy)propyl]amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-3-(2-methylphenoxy)propaneamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 473 (M⁺+1)

Example 891 N-[3-(2-Chlorophenoxy)propyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-3-(2-chlorophenoxy)propaneamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 466 (M⁺+1)

Example 892 N-[3-(2-Chlorophenoxy)propyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-3-(2-chlorophenoxy)propaneamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (156 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 893 N-[3-(2-Chlorophenoxy)propyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-3-(2-chlorophenoxy)propaneamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (156 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 894 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N-[2-(2,6-dimethylphenoxy)ethyl]-amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-2-(2,6-dimethylphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 473 (M⁺+1)

Example 895 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-N-[2-(2,6-dimethylphenoxy)ethyl]-amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-2-(2,6-dimethylphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (155 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 473 (M⁺+1)

Example 896 N-[2-(2,6-Dimethoxyphenoxy)ethyl]-N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-amine

N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylphenyl}-2-(2,6-dimethoxyphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (156 mg, yield 80%).

Mass spectrometry value (ESI-MS, m/z): 505 (M⁺+1)

Example 897 N-Benzoyl-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolveed in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (78 mg, yield 94%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.02 (s, 6H), 6.54 (d, J=5.12 Hz, 1H), 7.22 (d, J=8.78 Hz, 2H), 7.33-7.77 (m, 5H), 7.81 (t, J=3.42 Hz, 1H), 7.83-7.95 (m, 3H), 8.02 (d, J=8.76 Hz, 1H), 8.49 (d, J=5.12 Hz, 1H), 9.42 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 460 (M⁺+1)

Example 898 N-(2-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 2-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (83 mg, yield 100%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.07 (s, 6H), 6.57 (d, J=5.37 Hz, 1H), 7.23-7.29 (m, 3H), 7.44-7.47 (m, 2H), 7.53-7.54 (m, 3H), 7.79-7.86 (m, 3H), 8.53 (d, J=5.37 Hz, 1H), 9.23 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 899 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-fluorobenzoyl)thiourea

2-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (75 mg, yield 93%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.06 (s, 6H), 6.57 (d, J=5.37 Hz, 1H), 7.23-7.29 (m, 5H), 7.39 (m, 1H), 7.44 (s, 1H), 7.54 (s, 1H), 7.64-7.67 (m, 1H), 7.83 (d, J=9.03 Hz, 2H), 8.13 (m, 1H), 8.53 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 478 (M⁺+1)

Example 900 N-(2-Bromobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

2-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml). A solution of 2-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (85 mg, yield 93%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), δ 3.95 (s, 3H), 6.56 (d, J=5.12 Hz, 1H), 7.32 (d, J=8.30 Hz, 2H), 7.41 (d, J=5.61 Hz, 2H), 7.44-7.52 (m, 3H), 7.62 (t, J=7.19 Hz, 1H), 7.72 (d, J=7.81 Hz, 1H), 7.84 (d, J=8.78 Hz, 2H), 8.31 (s, 1H), 8.52 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 539 (M⁺+1)

Example 901 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-methoxybenzoyl)thiourea

2-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (83 mg, yield 96%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.11 (s, 3H), 4.13 (s, 3H), 4.17 (s, 3H), 6.77 (d, J=6.01 Hz, 1H), 7.19 (t, J=7.69 Hz, 1H), 7.26-7.29 (m, 6H), 7.61-7.65 (m, 2H), 7.99 (d, J=8.78 Hz, 1H), 8.13 (s, 1H), 8.24 (dd, J=1.83 Hz, J=7.93 Hz, 1H), 8.51 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 490 (M⁺+1)

Example 902 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[2-(trifluoromethyl)benzoyl]thiourea

2-(Trifluoromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-(trifluoromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-(trifluoromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (83 mg, yield 95%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.95 (s, 3H), 6.56 (d, J=5.12 Hz, 1H), 7.32 (d, J=8.78 Hz, 2H), 7.40 (s, 1H), 7.49 (s, 1H), 7.75-7.86 (m, 6H), 8.51 (d, J=5.12 Hz, 1H), 12.13 (s, 1H), 12.33 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 528 (M⁺+1)

Example 903 N-Benzoyl-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (76 mg, yield 80%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.04 (s, 3H), 4.06 (s, 3H), 6.64 (d, J=5.12 Hz, 1H), 7.04-7.07 (m, 2H), 7.26 (s, 2H), 7.45 (s, 1H), 7.48 (s, 1H), 7.57 (t, J=7.69 Hz, 1H), 7.68 (t, J=7.44 Hz, 1H), 7.93 (d, J=7.39 Hz, 2H), 8.46 (t, J=8.79 Hz, 1H), 8.57 (d, J=5.12 Hz, 1H), 9.22 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 478 (M⁺+1)

Example 904 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(2-methylbenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 2-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (66 mg, yield 85%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.58 (s, 3H), 4.08 (s, 3H), 4.12 (s, 3H), 6.72 (d, J=5.61 Hz, 1H), 7.08-7.12 (m, 2H), 7.26-7.36 (m, 3H), 7.47-7.59 (m, 3H), 7.82 (bs, 1H), 8.56 (d, J=5.85 Hz, 1H), 8.60 (m, 1H), 8.93 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 905 N-(2-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 2-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (63 mg, yield 80%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.04 (s, 3H), 4.06 (s, 3H), 6.64 (d, J=5.37 Hz, 1H), 7.04-7.08 (m, 2H), 7.27 (s, 1H), 7.43-7.47 (m, 3H), 7.53-7.55 (m, 2H), 7.83 (d, J=7.32 Hz, 1H), 8.48 (t, J=8.90 Hz, 1H), 8.57 (d, J=5.37 Hz, 1H), 9.39 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 512 (M⁺+1)

Example 906 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(2-fluorobenzoyl)thiourea

2-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (63 mg, yield 80%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.11 (s, 3H), 4.17 (s, 3H), 6.84 (d, J=6.59 Hz, 1H), 7.06-7.15 (m, 3H), 7.33-7.40 (m, 3H), 7.58-7.68 (m, 1H), 8.13 (bs, 2H), 8.58 (d, J=6.59 Hz, 1H), 8.73 (bs, 1H), 10.00 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 907 N-(2-Bromobenzoyl)-N′-[4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl]thiourea

2-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (73 mg, yield 83%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.92 (s, 3H), 3.96 (s, 3H), 6.67 (d, J=5.12 Hz, 1H), 7.16 (d, J=8.78 Hz, 1H), 7.37-7.52 (m, 5H), 7.62 (d, J=7.07 Hz, 1H), 7.72 (d, J=7.56 Hz, 1H), 8.11 (t, J=8.53 Hz, 1H), 8.55 (d, J=5.12 Hz, 1H), 12.20 (s, 1H), 12.26 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 557 (M⁺+1)

Example 908 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(2-iodobenzoyl)thiourea

2-Iodo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-iodo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-iodo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (86 mg, yield 90%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.96 (s, 3H), 6.66 (d, J=5.21 Hz, 1H), 7.14 (d, J=7.56 Hz, 1H), 7.26 (t, J=5.61 Hz, 1H), 7.34-7.53 (m, 5H), 7.93 (d, J=8.35 Hz, 1H), 8.16 (m, 1H), 8.54 (d, J=5.21 Hz, 1H), 12.14 (bs, 1H), 12.32 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 604 (M⁺+1)

Example 909 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(2-methoxybenzoyl)thiourea

2-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (56 mg, yield 70%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.96 (s, 3H), 4.03 (s, 3H), 6.67 (d, J=5.37 Hz, 1H), 7.11-7.47 (m, 4H), 7.58 (m, 1H), 7.68 (m, 1H), 7.78 (m, 1H), 7.93 (d, J=6.34 Hz, 1H), 8.14 (m, 1H), 8.56 (d, J=5.37 Hz, 1H), 11.39 (s, 1H), 12.44 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 910 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-[2-(trifluoromethyl)benzoyl]thiourea

2-(Trifluoromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-(trifluoromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-(trifluoromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (69 mg, yield 80%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.96 (s, 3H), 6.67 (d, J=5.12 Hz, 1H), 7.13 (m, 1H), 7.42-7.47 (m, 3H), 7.69-7.85 (m, 4H), 8.12 (m, 1H), 8.56 (d, J=5.12 Hz, 1H), 12.17 (s, 1H), 12.31 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 546 (M⁺+1)

Example 911 N-Benzoyl-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (64 mg, yield 85%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.09 (s, 3H), 4.10 (s, 3H), 6.59 (d, J=5.85 Hz, 1H), 7.27 (s, 1H), 7.34 (t, J=8.54 Hz, 1H), 7.54-7.61 (m, 4H), 7.68-7.72 (m, 2H), 7.92 (d, J=7.80 Hz, 2H), 8.01 (d, J=11.47 Hz, 1H), 8.53 (d, J=5.85 Hz, 1H), 9.13 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 478 (M⁺+1)

Example 912 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(2-methylbenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 2-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (55 mg, yield 70%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.58 (s, 3H), 4.11 (s, 3H), 4.16 (s, 3H), 6.71 (d, J=6.34 Hz, 1H), 7.36 (s, 1H), 7.37-7.40 (m, 3H), 7.50 (t, J=7.81 Hz, 1H), 7.57-7.64 (m, 3H), 8.06 (bs, 1H), 8.17 (d, J=9.50 Hz, 1H), 8.54 (d, J=6.34 Hz, 1H), 8.88 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 913 N-(2-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl]thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 2-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (61 mg, yield 75%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.06 (s, 3H), 4.07 (s, 3H), 6.48 (d, J=5.12 Hz, 1H), 7.26 (s, 1H), 7.31 (t, J=8.42 Hz, 1H), 7.44-7.58 (m, 6H), 7.79 (d, J=7.56 Hz, 1H), 8.03 (d, J=11.47 Hz, 1H), 8.53 (d, J=5.12 Hz, 1H), 9.33 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 512 (M⁺+1)

Example 914 N-(2-Bromobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

2-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (73 mg, yield 83%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.96 (s, 6H), 6.51 (d, J=5.12 Hz, 1H), 7.42-7.53 (m, 7H), 7.59-7.63 (m, 2H), 7.72 (d, J=7.80 Hz, 1H), 8.10 (d, J=8.10 Hz, 1H), 8.51 (d, J=8.51 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 557 (M⁺+1)

Example 915 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(2-iodobenzoyl)thiourea

2-Iodo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-iodo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-iodo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (86 mg, yield 90%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.25 (s, 6H), 6.50 (d, J=4.64 Hz, 1H), 7.11 (t, J=1.71 Hz, 1H), 7.24-7.52 (m, 6H), 7.61 (d, J=9.03 Hz, 1H), 7.84 (d, J=8.05 Hz, 1H), 7.93 (d, J=8.05 Hz, 1H), 8.14 (d, J=12.2 Hz, 1H), 8.49 (d, J=5.12 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 604 (M⁺+1)

Example 916 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(2-methoxybenzoyl)thiourea

2-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (65 mg, yield 80%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 4.03 (s, 9H), 6.95 (d, J=6.01 Hz, 1H), 7.18 (t, J=7.56 Hz, 1H), 7.31 (d, J=8.54 Hz, 1H), 7.53 (s, 1H), 7.63-7.75 (m, 4H), 7.93 (d, J=6.34 Hz, 1H), 8.21 (d, J=12.4 Hz, 1H), 8.83 (d, J=6.59 Hz, 1H), 11.35 (s, 1H), 12.72 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 917 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-[2-(trifluoromethyl)benzoyl]thiourea

2-(Trifluoromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-(trifluoromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-(trifluoromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (63 mg, yield 73%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.96 (s, 3H), 3.97 (s, 3H), 6.53 (d, J=6.34 Hz, 1H), 7.43 (s, 1H), 7.52 (t, J=9.15 Hz, 2H), 7.62-7.64 (m, 1H), 7.75-7.84 (m, 3H), 7.87-7.88 (m, 1H), 8.09 (d, J=14.6 Hz, 1H), 8.52 (d, J=5.37 Hz, 1H), 12.23 (bs, 1H), 12.37 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 546 (M⁺+1)

Example 918 N-Benzoyl-N′-{3-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (63 mg, yield 85%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.03 (s, 3H), 4.07 (s, 3H), 6.45 (d, J=5.37 Hz, 1H), 7.26 (s, 2H), 7.29 (d, J=8.78 Hz, 1H), 7.56-7.60 (m, 3H), 7.69 (t, J=7.44 Hz, 1H), 7.74 (dd, J=2.68 Hz, J=8.78 Hz, 1H), 7.92 (d, J=7.08 Hz, 2H), 8.11 (s, 1H), 8.57 (bs, 1H), 9.17 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 919 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-methylbenzoyl)thiourea

3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 2-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (69 mg, yield 90%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.51 (s, 3H), 4.06 (s, 3H), 4.07 (s, 3H), 6.42 (d, J=5.37 Hz, 1H), 7.28-7.36 (m, 4H), 7.47-7.59 (m, 4H), 7.75 (dd, J=2.44 Hz, 8.78 Hz, 1H), 8.11 (d, J=2.44 Hz, 1H), 8.50 (d, J=5.37 Hz, 1H), 8.92 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 509 (M⁺+1)

Example 920 N-(2-Chlorobenzoyl)-N′-{3-chloro-4-(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

3-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 2-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (79 mg, yield 90%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.43 (d, J=5.12 Hz, 1H), 7.43-7.59 (m, 5H), 7.64 (d, J=7.81 Hz, 1H), 7.76 (d, J=11.22 Hz, 1H), 8.19 (bs, 1H), 8.52 (d, 1H, J=5.37 Hz), 12.12 (bs, 1H), 12.38 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 530 (M⁺+1)

Example 921 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-fluorobenzoyl)thiourea

2-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (66 mg, yield 86%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.43 (d, J=5.12 Hz, 1H), 7.34-7.39 (m, 2H), 7.43 (s, 1H), 7.51 (t, J=9.15 Hz, 2H), 7.56-7.69 (m, 3H), 8.17 (bs, 1H), 8.52 (d, J=5.37 Hz, 1H), 11.79 (bs, 1H), 12.43 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 512 (M⁺+1)

Example 922 N-(2-Bromobenzoyl)-N′-{3-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

2-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (61 mg, yield 70%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.43 (d, J=5.12 Hz, 1H), 7.32-7.53 (m, 5H), 7.60 (d, J=5.86 Hz, 1H), 7.72-7.76 (m, 2H), 8.20 (bs, 1H), 8.51 (d, J=5.12 Hz, 1H), 12.12 (s, 1H), 12.39 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 573 (M⁺+1)

Example 923 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-methoxybenzoyl)thiourea

2-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (67 mg, yield 85%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 4.03 (s, 3H), 6.43 (d, J=5.37 Hz, 1H), 7.19 (t, J=7.32 Hz, 1H), 7.31 (d, J=8.05 Hz, 1H), 7.43 (s, 1H), 7.49-7.54 (m, 3H), 7.68 (t, J=8.78 Hz, 1H), 7.78 (dd, J=2.68 Hz, J=9.03 Hz, 1H), 7.93 (d, J=9.76 Hz, 1H), 8.52 (d, J=5.13 Hz, 1H), 11.33 (bs, 1H), 2.59 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 924 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[2-(trifluoromethyl)benzoyl]-thiourea

2-(Trifluoromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-(trifluoromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-(trifluoromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (61 mg, yield 85%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.42 (d, J=5.02 Hz, 1H), 7.42 (s, 1H), 7.48 (d, J=8.78 Hz, 1H), 7.53 (s, 1H), 7.75-7.87 (m, 6H), 8.19 (bs, 1H), 8.50 (d, J=5.12 Hz, 1H), 12.21 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 562 (M⁺+1)

Example 925 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-nitrophenyl}-N′-(2-methylbenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-nitroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 2-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (66 mg, yield 80%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.36 (s, 3H), 3.93 (s, 3H), 3.94 (s, 3H), 6.52 (d, J=5.37 Hz, 1H), 7.15-7.22 (m, 3H), 7.28-7.39 (m, 3H), 7.42 (dd, J=2.81 Hz, 9.15 Hz, 1H), 7.50 (s, 1H), 7.54 (s, 1H), 7.66 (bs, 1H), 7.81 (s, 1H), 8.46 (d, J=5.12 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 519 (M⁺+1)

Example 926 N-Benzoyl-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (69 mg, yield 89%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.09 (s, 3H), 4.11 (s, 3H), 7.23-7.34 (m, 4H), 7.55-7.59 (m, 4H), 7.68 (t, J=7.56 Hz, 1H), 7.88-7.93 (m, 3H), 8.69 (s, 1H), 9.12 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 461 (M⁺+1)

Example 927 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-methylbenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 2-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (72 mg, yield 90%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.50 (s, 3H), 3.98 (s, 3H), 3.99 (s, 3H), 7.29-7.38 (m, 7H), 7.42-7.46 (m, 1H), 7.52 (d, J=7.81. Hz, 1H), 7.57 (s, 1H), 7.80-7.82 (m, J=8.78 Hz, 2H), 8.56 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 475 (M⁺+1)

Example 928 N-(2-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 2-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (79 mg, yield 95%).

¹H-NMR (CDCl₃₁ 400 MHz): δ 3.98 (s, 3H), 3.99 (s, 3H), 7.37-7.40 (m, 3H), 7.45-7.49 (m, 1H), 7.53-7.58 (m, 3H), 7.65 (d, J=7.81 Hz, 1H), 7.79 (d, J=8.54 Hz, 2H), 8.58 (s, 1H), 12.04 (bs, 1H), 12.35 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 495 (M⁺+1)

Example 929 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-methoxybenzoyl)thiourea

2-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (74 mg, yield 90%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.97 (s, 3H), 4.03 (s, 3H), 4.05 (s, 3H), 6.81 (d, J=6.34 Hz, 1H), 7.11-7.12 (m, 1H), 7.17-7.23 (m, 2H), 7.31 (d, J=8.54 Hz, 1H), 7.53-7.80 (m, 3H), 7.88 (dd, J=2.56 Hz, 8.91 Hz, 1H), 7.81 (d, J=7.81 Hz, 1H), 8.30 (s, 1H), 8.81 (d, J=6.34 Hz, 1H), 11.4 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 491 (M⁺+1)

Example 930 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(3-methylbenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 3-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (77 mg, yield 96%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.48 (s, 3H), 4.08 (s, 3H), 4.11 (s, 3H), 6.65 (d, J=5.85 Hz, 1H), 7.23-7.29 (m, 2H), 7.43-7.58 (m, 3H), 7.61 (s, 1H), 7.72 (t, J=8.66 Hz, 3H), 7.89 (d, J=8.78 Hz, 2H), 8.51 (d, J=5.85 Hz, 1H), 9.13 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 931 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(3-fluorobenzoyl)thiourea

3-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (70 mg, yield 87%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.05 (s, 3H), 4.06 (s, 3H), 6.57 (d, J=5.12 Hz, 1H), 7.24-7.26 (m, 3H), 7.35-7.40 (m, 1H), 7.44 (s, 1H), 7.54-7.59 (m, 2H), 7.64-7.68 (m, 2H), 7.80-7.84 (m, 2H), 8.53 (d, J=5.12 Hz, 1H), 9.09 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 478 (M⁺+1)

Example 932 N-(3-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 3-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (77 mg, yield 93%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.05 (s, 3H), 4.06 (s, 3H), 6.58 (d, J=5.37 Hz, 1H), 7.24-7.92 (m, 11H), 8.52 (d, J=5.37 Hz, 1H), 9.13 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 933 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(3-methoxybenzoyl)thiourea

3-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (70 mg, yield 80%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.90 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.57 (d, J=5.37 Hz, 1H), 7.13-7.16 (m, 2H), 7.23-7.26 (m, 2H), 7.37-7.49 (m, 4H), 7.54 (s, 1H), 7.81-7.84 (m, 2H), 8.53 (d, J=5.37 Hz, 1H), 9.13 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 490 (M⁺+1)

Example 934 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[3-(trifluoromethyl)benzoyl]thiourea

3-(Trifluoromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-(trifluoromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-(trifluoromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (67 mg, yield 75%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.94 (s, 3H), 3.96 (s, 3H), 6.59 (d, J=5.37 Hz, 1H), 7.35 (d, J=8.78 Hz, 2H), 7.43 (s, 1H), 7.53 (s, 1H), 7.78-7.85 (m, 3H), 8.04 (d, J=8.05 Hz, 1H), 8.26 (d, J=8.05 Hz, 1H), 8.35 (s, 1H), 8.55 (d, J=5.37 Hz, 1H), 11.79 (s, 1H), 12.49 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 528 (M⁺+1)

Example 935 N-(3-Bromobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

3-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (67 mg, yield 74%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.05 (s, 3H), 4.06 (s, 3H), 6.66 (d, J=5.12 Hz, 1H), 7.24-7.26 (m, 3H), 7.44-7.47 (m, 2H), 7.53 (s, 1H), 7.80-7.84 (m, 4H), 8.07 (bs, 1H), 8.53 (d, J=5.12 Hz, 1H), 9.03 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 539 (M⁺+1)

Example 936 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(3-methylbenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 3-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (68 mg, yield 87%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.47 (s, 3H), 4.04 (s, 3H), 4.06 (s, 3H), 6.64 (d, J=5.12 Hz, 1H), 7.03-7.07 (m, 2H), 7.26 (s, 2H), 7.42-7.49 (in, 3H), 7.07-7.73 (m, 2H), 8.46 (t, J=8.90 Hz, 1H), 8.57 (d, J=5.12 Hz, 1H), 9.18 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 937 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(3-fluorobenzoyl)thiourea

3-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (71 mg, yield 90%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.96 (s, 3H), 6.67 (d, J=5.37 Hz, 1H), 7.38-7.73 (m, 6H), 7.84-7.86 (m, 1H), 8.05 (m, 2H), 8.29 (s, 1H), 8.56 (d, J=5.12 Hz, 1H), 11.9 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 938 N-(3-chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 3-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (76 mg, yield 93%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.04 (s, 3H), 4.06 (s, 3H), 6.63 (d, J=5.13 Hz, 1H), 6.65-7.07 (m, 2H), 7.26-7.27 (m, 1H), 7.45-7.53 (m, 3H), 7.65 (d, J=8.05 Hz, 1H), 7.80 (d, J=8.78 Hz, 1H), 7.94 (s, 1H), 8.44 (t, J=7.93 Hz, 1H), 8.57 (d, J=5.13 Hz, 1H), 9.17 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 512 (M⁺+1)

Example 939 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(3-methoxybenzoyl)thiourea

3-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (73 mg, yield 90%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.86 (s, 3H), 3.93 (s, 3H), 3.96 (s, 3H), 6.66 (d, J=5.12 Hz, 1H), 7.16 (d, J=7.32 Hz, 1H), 7.22-7.24 (m, 1H), 7.38-7.48 (m, 4H), 7.57-7.60 (m, 2H), 8.08 (t, J=8.91 Hz, 1H), 8.56 (d, J=5.12 Hz, 1H), 11.82 (bs, 1H), 12.55 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 940 N-(3-Bromobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

3-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (85 mg, yield 96%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.96 (s, 3H), 6.66 (d, J=4.88 Hz, 1H), 7.15 (d, J=9.51 Hz, 1H), 7.36-7.39 (m, 2H), 7.41 (s, 1H), 7.46 (s, 1H), 7.51 (t, J=7.81 Hz, 1H), 7.86 (d, J=7.81 Hz, 1H), 7.98 (d, J=7.56 Hz, 1H), 8.07 (m, 1H), 8.19 (s, 1H), 8.70 (d, J=5.12 Hz, 1H), 11.98 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 557 (M⁺+1)

Example 941 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(3-methylbenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 3-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (64 mg, yield 82%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.48 (s, 3H), 4.06 (s, 3H), 4.07 (s, 3H), 6.49 (d, J=4.39 Hz, 1H), 7.26 (s, 1H), 7.30 (t, J=8.54 Hz, 1H), 7.44-7.52 (m, 4H), 7.58 (s, 1H), 7.69-7.12 (m, 2H), 8.03 (dd, J=2.44 Hz, 11.71 Hz, 1H), 8.53 (d, J=5.37 Hz, 1H), 9.13 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 942 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(3-fluorobenzoyl)thiourea

3-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (65 mg, yield 83%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.10 (s, 3H), 4.15 (s, 3H), 6.68 (d, J=6.01 Hz, 1H), 7.27 (m, 2H), 7.35-7.42 (m, 2H), 7.57-7.69 (m, 4H), 7.98 (bs, 1H), 8.12 (m, 1H), 8.54 (d, J=6.34 Hz, 1H), 9.11 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 943 N-(3-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 3-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (73 mg, yield 90%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.09 (s, 3H), 4.11 (s, 3H), 6.60 (d, J=5.61 Hz, 1H), 7.26 (s, 1H), 7.35 (t, J=8.54 Hz, 1H), 7.51-7.56 (m, 2H), 7.61 (s, 1H), 7.65-7.68 (m, 1H), 7.77-7.79 (m, 2H), 7.91-7.92 (m, 1H), 8.08 (dd, J=2.68 Hz, 11.47 Hz, 1H), 8.53 (d, J=5.61 Hz, 1H), 9.08 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 512 (M⁺+1).

Example 944 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(3-methoxybenzoyl)thiourea

3-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (73 mg, yield 90%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.99 (s, 3H), 4.13 (s, 3H), 4.17 (s, 3H), 6.87 (d, J=5.61 Hz, 1H), 7.18 (dd, J=2.44 Hz, 8.29 Hz, 1H), 7.31-7.46 (m, 2H), 7.55-7.62 (m, 4H), 7.71 (s, 1H), 7.84 (s, 1H), 8.23 (dd, J=2.44 Hz, 11.95 Hz, 1H), 8.67 (d, J=6.59 Hz, 1H), 11.00 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 945 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-[3-(trifluoromethyl)benzoyl]thiourea

3-(Trifluoromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-(trifluoromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-(trifluoromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (77 mg, yield 89%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.96 (s, 6H), 6.54 (d, J=5.37 Hz, 1H), 7.43 (s, 1H), 7.53-7.60 (m, 4H), 7.80 (t, J=8.05 Hz, 1H), 8.02-8.10 (m, 2H), 8.26 (d, J=7.81 Hz, 1H), 8.35 (s, 1H), 8.53 (d, J=4.88 Hz, 1H), 12.03 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 546 (M⁺+1)

Example 946 N-(3-Bromobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

3-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (79 mg, yield 90%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.96 (s, 6H), 6.51 (d, J=5.37 Hz, 1H), 7.41 (s, 1H), 7.48-7.60 (m, 5H), 7.86 (d, J=7.56 Hz, 1H), 7.97 (d, J=8.05 Hz, 1H), 8.08 (d, J=12.44 Hz, 1H), 8.18 (s, 1H), 8.50 (d, J=5.37 Hz, 1H), 11.84 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 557 (M⁺+1)

Example 947 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(3-methylbenzoyl)thiourea

3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 3-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (71 mg, yield 92%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.48 (s, 3H), 4.07 (s, 6H), 6.44 (d, J=5.61 Hz, 1H), 7.26 (s, 3H), 7.29 (d, J=8.78 Hz, 1H), 7.43-7.50 (m, 2H), 7.59 (s, 1H), 7.69-7.74 (m, 3H), 8.11 (d, J=2.44 Hz, 1H), 9.14 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 509 (M⁺+1)

Example 948 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(3-fluorobenzoyl)thiourea

3-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (64 mg, yield 83%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.43 (d, J=5.12 Hz, 1H), 7.43 (s, 3H), 7.49-7.54 (m, 2H), 7.59-7.62 (m, 1H), 7.75 (d, J=8.78 Hz, 1H), 7.82-7.86 (m, 1H), 8.18 (bs, 1H), 8.51 (d, J=5.12 Hz, 1H), 11.79 (bs, 1H), 12.43 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 512 (M⁺+1)

Example 949 N-(3-Chlorobenzoyl)-N′-[3-chloro-4-(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 3-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (77 mg, yield 97%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.06 (s, 3H), 4.07 (s, 3H), 6.46 (d, J=5.37 Hz, 1H), 7.29-7.32 (m, 4H), 7.52 (t, J=7.93 Hz, 1H), 7.61 (s, 1H), 7.64-7.66 (m, 1H), 7.71 (dd, J=2.68 Hz, 8.78 Hz, 1H), 7.87 (d, J=7.81 Hz, 1H), 8.00 (s, 1H), 8.07 (d, J=2.44 Hz, 1H), 8.51 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 950 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(3-methoxybenzoyl)thiourea

3-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (65 mg, yield 82%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.86 (s, 3H), 3.95 (s, 3H), 3.96 (s, 3H), 6.41 (d, J=5.12 Hz, 1H), 7.22 (d, J=8.54 Hz, 1H), 7.41-7.60 (m, 8H), 7.74 (d, J=8.78 Hz, 1H), 8.12 (bs, 1H), 8.50 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 951 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[3-(trifluoromethyl)benzoyl]-thiourea

3-(Trifluoromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-(trifluoromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]-aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-(trifluoromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (75 mg, yield 88%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.43 (d, J=5.37 Hz, 1H), 7.42 (s, 1H), 7.49-7.53 (m, 2H), 7.74 (d, J=9.27 Hz, 1H), 7.80 (t, J=8.05 Hz, 1H), 8.03 (d, J=7.56 Hz, 1H), 8.18 (s, 1H), 8.26 (d, J=5.37 Hz, 1H), 8.35 (s, 1H), 8.51 (d, J=5.37 Hz, 1H), 12.04 (s, 1H), 12.52 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 562 (M⁺+1)

Example 952 N-(3-Bromobenzoyl)-N′-{3-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

3-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (81 mg, yield 93%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 4.05 (s, 3H), 4.06 (s, 3H), 6.85 (d, J=6.34 Hz, 1H), 7.50-7.54 (m, 2H), 7.66 (d, J=8.78 Hz, 1H), 7.76 (s, 1H), 7.85-7.89 (m, 2H), 7.98 (d, J=7.80 Hz, 1H), 8.19 (s, 1H), 8.28 (s, 1H), 8.84 (d, J=6.34 Hz, 1H), 11.8 (s, 1H), 12.56 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 573 (M⁺+1)

Example 953 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-nitrophenyl}-N′-(3-methylbenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-nitroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 3-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (69 mg, yield 91%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.47 (s, 3H), 4.04 (s, 3H), 4.07 (s, 3H), 6.67 (d, J=5.37 Hz, 1H), 7.26 (s, 2H), 7.43-7.51 (m, 4H), 7.73 (d, J=7.32 Hz, 1H), 7.77 (s, 1H), 7.94 (d, J=2.68 Hz, 1H), 8.52 (d, J=9.03 Hz, 1H), 8.61 (d, J=5.12 Hz, 1H), 9.24 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 519 (M⁺+1)

Example 954 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(3-methylbenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 3-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (76 mg, yield 95%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.47 (s, 3H), 4.12 (s, 3H), 4.17 (s, 3H), 7.26-7.34 (m, 5H), 7.45-7.47 (m, 1H), 7.61 (s, 1H), 7.71 (m, 2H), 7.93 (d, J=9.03 Hz, 2H), 8.77 (s, 1H), 9.10 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 475 (M⁺+1)

Example 955 N-(3-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 3-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (80 mg, yield 96%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.08 (s, 6H), 7.29 (s, 2H), 7.33 (d, J=8.78 Hz, 1H), 7.41 (s, 1H), 7.50 (t, J=7.81 Hz, 1H), 7.57 (s, 1H), 7.63 (d, J=7.32 Hz, 1H), 7.83-7.86 (m, 3H), 7.98 (s, 1H), 8.65 (s, 1H), 9.71 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 495 (M⁺+1)

Example 956 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(3-methoxybenzoyl)thiourea

3-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (67 mg, yield 81%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.87 (s, 3H), 3.98 (s, 3H), 3.99 (s, 3H), 7.21-7.23 (m, 1H), 7.28-7.39 (m, 3H), 7.46 (t, J=7.93 Hz, 1H), 7.56-7.60 (m, 3H), 7.79 (d, J=8.78 Hz, 2H), 8.56 (s, 1H), 11.59 (s, 1H), 12.66 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 491 (M⁺+1)

Example 957 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[3-(trifluoromethyl)benzoyl]thiourea

3-(Trifluoromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-(trifluoromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-(trifluoromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (75 mg, yield 85%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.97 (s, 3H), 3.99 (s, 3H), 7.38-7.44 (m, 3H), 7.58 (s, 1H), 7.78-7.82 (m, 3H), 8.04 (d, J=8.05 Hz, 1H), 8.26 (d, J=7.81 Hz, 1H), 8.36 (s, 1H), 8.56 (s, 1H), 11.97 (s, 1H), 12.95 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 958 N-(3-Bromobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

3-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (6.1 mg, yield 70%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.98 (s, 3H), 3.99 (s, 3H), 7.37-7.40 (m, 3H), 7.52 (t, J=7.93 Hz, 1H), 7.58 (s, 1H), 7.78 (d, J=8.78 Hz, 2H), 7.87 (d, J=7.08 Hz, 1H), 7.97 (d, J=7.81 Hz, 1H), 8.18 (s, 1H), 8.58 (s, 1H), 11.89 (bs, 1H), 12.48 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 540 (M⁺+1)

Example 959 N-{4-[(6,7-Dimethoxy-4-quinolyl)-oxy]phenyl}-N′-(4-methylbenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (70 mg, yield 89%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.48 (s, 3H), 4.09 (s, 3H), 4.15 (s, 3H), 6.72 (d, J=6.34 Hz, 1H), 7.23-7.29 (m, 3H), 7.37 (d, J=7.81 Hz, 2H), 7.62 (s, 1H), 7.82 (d, J=8.05 Hz, 2H), 7.94 (d, J=9.03 Hz, 2H), 7.98 (s, 1H), 8.51 (d, J=5.12 Hz, 1H), 9.12 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 960 N-(4-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (77 mg, yield 92%).

¹H-NMR (CDCl₃₁ 400 MHz): δ 4.06 (s, 3H), 4.07 (s, 3H), 6.59 (d, J=5.37 Hz, 1H), 7.24-7.30 (m, 3H), 7.46-7.56 (m, 4H), 7.76-7.88 (m, 4H), 8.53 (d, J=5.37 Hz, 1H), 9.08 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 494 (M⁺+1)

Example 961 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(4-fluorobenzoyl)thiourea

4-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (69 mg, yield 85%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.05 (s, 3H), 4.06 (s, 3H), 6.57 (d, J=5.12 Hz, 1H), 7.24-7.26 (m, 5H), 7.44 (s, 1H), 7.54 (s, 1H), 7.80-7.83 (m, 2H), 7.95 (m, 2H), 8.53 (d, J=5.37 Hz, 1H), 9.09 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 478 (M⁺+1)

Example 962 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(4-nitrobenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-nitro-1-benzenecarbonyl isothiocyanate (30 mg) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (80 mg, yield 94%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.06 (s, 3H), 4.08 (s, 3H), 6.59 (d, J=5.37 Hz, 1H), 7.24-7.30 (m, 5H), 7.50 (s, 1H), 7.54 (s, 1H), 7.82-7.85 (m, 2H), 8.01-8.12 (m, 2H), 8.41-8.43 (m, 2H), 8.53 (d, J=5.37 Hz, 1H), 9.16 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 507 (M⁺+1)

Example 963 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(4-methoxybenzoyl)thiourea

4-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (67 mg, yield

¹H-NMR (CDCl₃, 400 MHz): δ 3.92 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.57 (d, J=5.37 Hz, 1H), 7.02-7.04 (m, 2H), 7.23-7.26 (m, 3H), 7.44 (s, 1H), 7.54 (s, 1H), 7.77-7.85 (m, 2H), 7.88-7.90 (m, 2H), 8.53 (d, J=5.37 Hz, 1H), 9.07 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 490 (M⁺+1)

Example 964 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(4-methylbenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (77 mg, yield 98%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.47 (s, 3H), 4.04 (s, 3H), 4.06 (s, 3H), 6.64 (d, J=5.37 Hz, 1H), 7.04-7.07 (m, 2H), 7.26 (s, 1H), 7.36 (d, J=8.54 Hz, 2H), 7.46 (d, J=11.95 Hz, 2H), 7.83 (d, J=8.29 Hz, 2H), 8.46 (t, J=8.90 Hz, 1H), 8.56 (d, J=5.12 Hz, 1H), 9.18 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 965 N-(4-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (77 mg, yield 94%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.04 (s, 3H), 4.06 (s, 3H), 6.64 (d, J=5.12 Hz, 1H), 7.04-7.07 (m, 2H), 7.26 (s, 1H), 7.45-7.46 (m, 2H), 7.54-7.56 (m, 2H), 7.87-7.89 (m, 2H), 8.39 (t, J=8.78 Hz, 1H), 8.57 (d, J=5.37 Hz, 1H), 9.17 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 512 (M⁺+1)

Example 966 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(4-fluorobenzoyl)thiourea

4-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (65 mg, yield 83%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.96 (s, 3H), 6.62 (d, J=5.37 Hz, 1H), 7.17 (d, J=11.2 Hz, 1H), 7.36-7.47 (m, 5H), 8.05-8.11 (m, 3H), 8.56 (d, J=5.12 Hz, 1H), 11.88 (s, 1H), 12.48 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 967 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(4-iodobenzoyl)thiourea

4-Iodo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-iodo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-iodo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (92 mg, yield 96%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.96 (s, 3H), 4.03 (s, 3H), 6.67 (d, J=4.88 Hz, 1H), 7.17 (d, J=8.29 Hz, 2H), 7.39-7.47 (m, 2H), 7.77 (d, J=8.05 Hz, 2H), 7.94 (d, J=8.29 Hz, 2H), 8.06 (t, J=8.54 Hz, 1H), 8.56 (d, J=5.12 Hz, 1H), 11.90 (s, 1H), 12.44 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 604 (M⁺+1)

Example 968 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(4-nitrobenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-nitro-1-benzenecarbonyl isothiocyanate (30 mg) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (75 mg, yield 90%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.04 (s, 3H), 4.06 (s, 3H), 6.64 (dd, J=3.42 Hz, J=5.12 Hz, 1H), 7.05-7.08 (m, 2H), 7.25-7.26 (m, 2H), 7.45 (dd, J=3.17 Hz, 6.59 Hz, 2H), 8.12 (dd, J=2.93 Hz, 8.66 Hz, 2H), 8.39-8.45 (m, 3H), 8.57 (dd, J=3.42 Hz, J=5.12 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 969 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(4-methoxybenzoyl)thiourea

4-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (71 mg, yield 88%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.92 (s, 3H), 4.04 (s, 3H), 4.02 (s, 3H), 6.64 (d, J=5.12 Hz, 1H), 7.02-7.06 (m, 4H), 7.26 (s, 1H), 7.46 (d, J=12.06 Hz, 2H), 7.90 (d, J=9.03 Hz, 2H), 8.46 (t, J=9.03 Hz, 1H), 8.56 (d, J=5.12 Hz, 1H), 9.14 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 970 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(4-methylbenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (77 mg, yield 98%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.46 (s, 3H), 4.09 (s, 3H), 4.10 (s, 3H), 6.57 (d, J=5.37 Hz, 1H)/7.26-7.38 (m, 4H), 7.54 (d, J=8.54 Hz, 1H), 7.59 (s, 1H), 7.68 (s, 1H), 7.81 (d, J=8.29 Hz, 2H), 8.08 (dd, J=2.47 Hz, J=11.47 Hz, 1H), 8.53 (d, J=5.61 Hz, 1H), 9.09 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 971 N-(4-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (78 mg, yield 96%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.06 (s, 3H), 4.07 (s, 3H), 6.49 (d, J=5.12 Hz, 1H), 7.26 (s, 1H), 7.31 (t, J=8.66 Hz, 1H), 7.44 (s, 1H), 7.50 (d, J=8.78 Hz, 1H), 7.55-7.57 (m, 3H), 7.86-7.88 (m, 2H), 8.00 (dd, J=2.44 Hz, J=11.47 Hz, 1H), 8.52 (d, J=5.12 Hz, 1H), 9.11 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 512 (M⁺+1)

Example 972 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(4-fluorobenzoyl)thiourea

4-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (68 mg, yield 86%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.11 (s, 3H), 4.15 (s, 3H), 6.68 (d, J=6.34 Hz, 1H), 7.25-7.29 (m, 3H), 7.37 (t, J=8.54 Hz, 1H), 7.58 (d, J=9.76 Hz, 1H), 7.63 (s, 1H), 7.95-7.98 (m, 3H), 8.12 (dd, J=2.56 Hz, J=11.59 Hz, 1H), 8.54 (d, J=6.01 Hz, 1H), 9.09 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 973 N-(4-Bromobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

4-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (81 mg, yield 91%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.96 (s, 6H), 6.52 (d, J=5.37 Hz, 1H), 7.42 (s, 1H), 7.49-7.59 (m, 3H), 7.76 (d, J=8.54 Hz, 2H), 7.94 (d, J=8.54 Hz, 2H), 8.08 (d, J=11.95 Hz, 1H), 8.51 (d, J=5.12 Hz, 1H), 11.79 (s, 1H), 12.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 557 (M⁺+1)

Example 974 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(4-iodobenzoyl)thiourea

4-Iodo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-iodo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-iodo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (84 mg, yield 88%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.96 (s, 5H), 6.52 (d, J=5.37 Hz, 1H), 7.42-7.61 (m, 5H), 7.77 (d, J=7.07 Hz, 2H), 7.85 (d, J=8.29 Hz, 2H), 8.11 (d, J=8.54 Hz, 3H), 8.51 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 604 (M⁺+1)

Example 975 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(4-nitrobenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-nitro-1-benzenecarbonyl isothiocyanate (30 mg) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (79 mg, yield 96%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.11 (s, 3H), 4.17 (s, 3H), 6.75 (m, 1H), 7.29 (s, 2H), 7.40 (t, J=8.54 Hz, 1H), 7.57 (m, 1H), 7.65 (s, 1H), 7.94 (s, 1H), 8.10 (d, J=11.47 Hz, 1H), 8.18-8.21 (m, 2H), 8.40-8.43 (m, 2H), 8.62 (d, J=6.34 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 976 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(4-methoxybenzoyl)thiourea

4-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (70 mg, yield 87%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.87 (s, 3H), 3.96 (s, 6H), 6.52 (d, J=5.12 Hz, 1H), 7.09 (d, J=8.78 Hz, 2H), 7.43 (s, 1H), 7.49-7.54 (m, 2H), 7.61 (d, J=8.78 Hz, 1H), 8.03-8.11 (m, 3H), 8.52 (d, J=5.37 Hz, 1H), 11.52 (bs, 1H), 12.82 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 977 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(4-methylbenzoyl)thiourea

3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (76 mg, yield 99%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.47 (s, 3H), 4.07 (s, 6H), 6.43 (d, J=5.37 Hz, 1H), 7.26 (s, 2H), 7.29 (d, J=8.78 Hz, 2H), 7.37 (d, J=8.05 Hz, 2H), 7.59 (s, 1H), 7.73 (dd, J=2.44 Hz, J=8.78 Hz, 1H), 7.81 (d, J=8.29 Hz, 2H), 8.10 (d, J=2.44 Hz, 1H), 9.13 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 509 (M⁺+1)

Example 978 N-(4-Chlorobenzoyl)-N′-[3-chloro-4-(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (74 mg, yield 93%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.04 (s, 3H), 4.07 (s, 3H), 6.44 (d, J=5.37 Hz, 1H), 7.29-7.32 (m, 3H), 7.54-7.60 (m, 4H), 7.71 (dd, J=2.68 Hz, J=8.78 Hz, 1H), 7.93-7.95 (m, 2H), 8.07 (d, J=2.44 Hz, 1H), 8.53 (d, J=5.34 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 979 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(4-fluorobenzoyl)thiourea

4-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (67 mg, yield 87%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.06 (s, 3H), 4.07 (s, 3H), 6.42 (d, J=5.37 Hz, 1H), 7.05-7.29 (m, 4H), 7.45 (s, 1H), 7.58 (s, 1H), 7.71 (dd, J=2.44 Hz, J=8.78. Hz, 1H), 7.94-7.98 (m, 2H), 8.08 (d, J=2.44 Hz, 1H), 8.52 (d, J=5.37 Hz, 1H), 9.12 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 512 (M⁺+1)

Example 980 N-(4-Bromobenzoyl)-N′-{3-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

4-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (80 mg, yield 83%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.43 (d, J=5.12 Hz, 1H), 7.43 (s, 1H), 7.51 (d, J=8.54 Hz, 1H), 7.54 (s, 1H), 7.65-7.85 (m, 3H), 7.93 (d, J=8.54 Hz, 2H), 8.31 (bs, 1H), 8.51 (d, J=5.12 Hz, 1H), 11.81 (bs, 1H), 12.53 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 573 (M⁺+1)

Example 981 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(4-iodobenzoyl)thiourea

4-Iodo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-iodo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-iodo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (94 mg, yield 90%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.43 (d, J=5.12 Hz, 1H), 7.43 (s, 1H), 7.49-7.54 (m, 2H), 7.66 (d, J=8.05 Hz, 1H), 7.75-7.77 (m, 2H), 7.89-7.96 (m, 2H), 8.18 (s, 1H), 8.51 (d, J=5.37 Hz, 1H), 11.77 (s, 1H), 12.54 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 620 (M⁺+1)

Example 982 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(4-nitrobenzoyl)thiourea

3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-nitro-1-benzenecarbonyl isothiocyanate (30 mg) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (78 mg, yield 95%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.08 (s, 6H), 6.45 (d, J=5.37 Hz, 1H), 7.31-7.33 (m, 3H), 7.46 (s, 1H), 7.61 (s, 1H)7.69-7.72 (m, 1H), 8.07 (d, J=2.44 Hz, 1H), 8.19-8.21 (m, 2H), 8.39-8.42 (m, 2H), 8.48 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 539 (M⁺+1)

Example 983 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(4-methoxybenzoyl)thiourea

4-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (68 mg, yield 86%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.92 (s, 3H), 4.08 (s, 6H), 6.47 (d, J=5.61 Hz, 1H), 7.04-7.05 (m, 2H), 7.31-7.34 (m, 3H), 7.52 (bs, 1H), 7.62 (s, 1H), 7.73 (dd, J=2.44 Hz, 8.78 Hz, 1H), 7.97 (d, J=9.03 Hz, 2H), 8.09 (d, J=2.68 Hz, 1H), 8.50 (d, J=5.38 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 524 (M⁺+1)

Example 984 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(4-methylbenzoyl)thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (73 mg, yield 92%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.47 (s, 3H), 4.09 (s, 3H), 4.12 (s, 3H), 7.26-7.37 (m, 5H), 7.58-7.62 (m, 2H), 7.81 (d, J=8.29 Hz, 2H), 7.89 (d, J=8.93 Hz, 2H), 8.69 (s, 1H), 9.09 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 475 (M⁺+1)

Example 985 N-(4-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (82 mg, yield 98%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.98 (s, 3H), 3.99 (s, 3H), 7.36-7.40 (m, 3H), 7.58-7.63 (m, 3H), 7.78 (d, J=8.54 Hz, 2H), 8.01 (d, J=8.29 Hz, 2H), 8.58 (s, 1H), 11.71 (bs, 1H), 1.2.50 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 495 (M⁺+1)

Example 986 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(4-fluorobenzoyl)thiourea

4-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (64 mg, yield 80%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.98 (s, 3H), 3.99 (s, 3H), 7.36-7.40 (m, 5H), 7.57 (s, 1H), 7.79 (d, J=8.78 Hz, 2H), 8.07-8.11 (m, 2H), 8.57 (s, 1H), 11.65 (s, 1H), 12.58 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 479 (M⁺+1)

Example 987 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(4-nitrobenzoyl)thiourea

4-Nitro-1-benzenecarbonyl isothiocyanate (30 mg) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (74 mg, yield 87%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.11 (s, 3H), 4.14 (s, 3H), 7.26 (s, 1H), 7.34 (d, J=8.78 Hz, 2H), 7.59 (s, 1H), 7.72 (bs, 1H), 7.89 (d, J=8.78 Hz, 2H), 8.12 (d, J=8.78 Hz, 2H), 8.42 (d, J=8.41 Hz, 2H), 8.72 (s, 1H), 9.19 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 988 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(4-methoxybenzoyl)thiourea

4-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (71 mg, yield 86%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.95 (s, 3H), 4.09 (s, 3H), 4.12 (s, 3H), 7.03 (d, J=9.03 Hz, 2H), 7.26-7.33 (m, 3H), 7.58-7.63 (m, 2H), 7.89 (d, J=9.03 Hz, 4H), 8.69 (s, 1H), 9.05 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 491 (M⁺+1)

Example 989 N-(1,3-Benzodioxol-5-ylcarbonyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

1,3-Benzodioxole-5-carbonyl isothiocyanate was prepared using commercially available 1,3-benzodioxole-5-carbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 1,3-benzodioxole-5-carbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (68 mg, yield 86%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.93 (s, 3H), 3.95 (s, 3H), 6.15 (s, 2H), 6.56 (d, J=5.37 Hz, 1H), 7.08 (d, J=8.29 Hz, 1H), 7.32 (d, J=8.78 Hz, 2H), 7.41 (s, 1H), 7.51 (s, 1H), 7.52 (s, 1H), 7.67 (d, J=8.30 Hz, 1H), 7.82 (d, J=8.54 Hz, 2H), 8.52 (d, J=5.37 Hz, 1H), 11.39 (bs, 1H), 12.65 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 504 (M⁺+1)

Example 990 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(4-ethoxybenzoyl)thiourea

4-Ethoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-ethoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-ethoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (76 mg, yield 92%).

Mass spectrometry value (ESI-MS, m/z): 554 (M⁺+1)

Example 991 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(4-phenylbenzoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-phenylbenzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-phenyl-1-benzenecarbonyl isothiocyanate was prepared using the resultant 4-phenyl-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-phenyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (76 mg, yield 92%).

Mass spectrometry value (ESI-MS, m/z): 554 (M⁺+1)

Example 992 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(4-ethoxybenzoyl)thiourea

4-Ethoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-ethoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-ethoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (72 mg, yield 89%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.38 (t, J=6.95 Hz, 3H), 3.95 (s, 3H), 3.96 (s, 3H), 4.14 (dd, J=7.08 Hz, 13.93 Hz, 2H), 6.41 (d, J=5.12 Hz, 1H), 7.05 (d, J=8.78 Hz, 2H), 7.42 (s, 1H), 7.47 (d, J=8.78 Hz, 1H), 7.53 (s, 2H), 7.26-7.75 (m, 1H), 8.02 (d, J=8.78 Hz, 2H), 8.19 (bs, 1H), 8.50 (d, J=5.37 Hz, 1H), 11.51 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 539 (M⁺+1)

Example 993 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(4-ethylbenzoyl)thiourea

4-Ethyl-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-ethyl-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-ethyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (69 mg, yield 87%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.21-1.24 (m, 3H), 2.69-2.72 (m, 2H), 3.93 (s, 3H), 3.96 (s, 3H), 6.65 (m, 1H), 7.14 (m, 1H), 7.38-7.47 (m, 7H), 7.95-7.97 (m, 2H), 8.11 (m, 1H), 8.55-8.56 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 994 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(4-propylbenzoyl)thiourea

4-Propyl-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-propyl-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-propyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (74 mg, yield 90%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.92 (t, J=7.08 Hz, 3H), 1.63-1.65 (m, 2H), 2.66 (m, 2H), 3.93 (s, 3H), 3.96 (s, 3H), 6.67 (m, 1H), 7.17 (m, 1H), 7.36-7.47 (m, 5H), 7.95 (d, J=8.05 Hz, 2H), 8.09 (m, 1H), 8.31 (s, 1H), 8.55 (d, J=5.37 Hz, 1H), 11.71 (s, 1H), 12.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 520 (M⁺+1)

Example 995 N-(4-Butylbenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

4-Butyl-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-butyl-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-butyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (68 mg, yield 80%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.92 (t, J=7.44 Hz, 3H), 1.30-1.36 (m, 2H), 1.58-1.62 (m, 2H), 2.68 (t, J=7.69 Hz, 3H), 3.93 (s, 3H), 3.96 (s, 3H), 6.57 (d, J=5.12 Hz, 1H), 7.16 (d, J=9.27 Hz, 1H), 7.36-7.47 (m, 5H), 7.95 (d, J=8.29 Hz, 2H), 8.11 (t, J=9.03 Hz, 1H), 8.29 (s, 1H), 8.55 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 996 N-[4-(Chloromethyl)benzoyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

4-(Chloromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-(chloromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-(chloromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (68 mg, yield 80%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.96 (s, 3H), 3.99 (s, 3H), 4.44-4.45 (m, 2H), 6.76 (d, J=5.61 Hz, 1H), 7.22 (d, J=5.61 Hz, 1H), 7.46-7.60 (m, 4H), 7.93-7.95 (m, 1H), 8.03-8.05 (m, 1H), 8.14 (m, 1H), 8.34 (s, 1H), 8.65 (d, J=5.61 Hz, 1H), 11.88 (s, 1H)₇ 12.55 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 526 (M⁺+1)

Example 997 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(4-ethylbenzoyl)thiourea

4-Ethyl-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-ethyl-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-ethyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (68 mg, yield 84%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.23 (t, J=7.50 Hz, 3H), 2.71 (dd, J=7.56 Hz, J=15.13 Hz, 2H), 3.96 (s, 6H), 6.51 (d, J=4.88 Hz, 1H), 7.39 (d, J=8.29 Hz, 2H), 7.42 (s, 1H), 7.50 (t, J=8.90 Hz, 1H), 7.54 (s, 1H), 7.61 (d, J=9.27 Hz, 1H), 7.95 (d, J=8.05 Hz, 2H), 8.10 (d, J=10.25 Hz, 1H), 8.51 (d, J=5.37 Hz, 1H), 11.40 (s, 1H), 12.50 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 998 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(4-propylbenzoyl)thiourea

4-Propyl-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-propyl-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-propyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (71 mg, yield 86%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.89-0.93 (m, 3H), 1.63-1.65 (m, 2H), 2.66 (m, 2H), 3.96 (s, 6H), 6.52 (m, 1H), 7.37-7.61 (m, 6H), 7.95 (d, J=6.83 Hz, 2H), 8.11 (m, 1H), 8.51 (d, J=5.12 Hz, 1H), 11.59 (s, 1H), 12.76 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 520 (M⁺+1)

Example 999 N-(4-Butylbenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

4-Butyl-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-butyl-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-butyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (66 mg, yield 78%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.92 (t, J=7.20 Hz, 3H), 1.32-1.36 (m, 2H), 1.58-1.62 (m, 2H), 2.68 (t, J=7.32 Hz, 2H), 3.96 (s, 6H), 6.51 (d, J=5.37 Hz, 1H), 7.36-7.59 (m, 7H), 7.94 (d, J=8.05 Hz, 2H), 8.10 (d, J=12.9 Hz, 1H), 8.30 (s, 1H), 8.51 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 1000 N-[4-(Chloromethyl)benzoyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

4-(Chloromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-(chloromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-(chloromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (68 mg, yield 81%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 4.02 (s, 6H), 4.45 (s, 2H), 6.84 (m, 1H), 7.54-7.70 (m, 6H), 8.03 (d, J=6.83 Hz, 2H), 8.19 (m, 2H), 8.74 (m, 1H), 11.75 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 526 (M⁺+1)

Example 1001 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(4-propylbenzoyl)thiourea

4-Propyl-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-propyl-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-propyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (47 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.92-0.96 (m, 3H), 1.64-1.69 (m, 2H), 2.65-2.69 (m, 2H), 4.03 (s, 3H), 4.05 (s, 3H), 6.76 (bs, 1H), 7.34-7.36 (m, 3H), 7.70-7.72 (m, 1H), 7.81-7.83 (m, 1H), 7.96-8.01 (m, 3H), 8.23 (s, 1H), 8.28 (s, 1H), 11.08 (s, 1H), 11.57 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 537 (M⁺+1)

Example 1002 N-[4-(Chloromethyl)benzoyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

4-(Chloromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-(chloromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-(chloromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (77 mg, yield 90%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.98 (s, 3H), 3.99 (s, 3H), 4.44 (d, J=5.86 Hz, 2H), 7.36-7.39 (m, 2H), 7.54-7.59 (m, 4H), 7.78-7.81 (m, 2H), 7.94 (d, J=8.29 Hz, 2H), 8.03 (d, J=8.29 Hz, 2H), 8.57 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 509 (M⁺+1)

Example 1003 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2,4-dimethylbenzoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,4-dimethylbenzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,4-dimethyl-1-benzenecarbonyl isothiocyanate was prepared using the resultant 2,4-dimethyl-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,4-dimethyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (77 mg, yield 93%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.45 (s, 3H), 2.49 (s, 3H), 3.94 (s, 3H), 3.96 (s, 3H), 6.51-6.57 (m, 1H), 7.08-7.11 (m, 1H), 7.25-7.50 (m, 7H), 7.83-7.84 (m, 2H), 8.46-8.51 (m, 1H), 11.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 1004 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2,5-dimethylbenzoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,5-dimethylbenzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,5-dimethyl-1-benzenecarbonyl isothiocyanate was prepared using the resultant 2,5-dimethyl-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,5-dimethyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (75 mg, yield 91%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.33 (s, 3H), 2.39 (s, 3H), 3.93 (s, 3H), 3.96 (s, 3H), 6.56 (d, J=5.37 Hz, 1H), 7.18-7.36 (m, 7H), 7.39 (s, 1H), 7.50 (s, 1H), 7.83-7.86 (m, 2H), 8.51 (d, J=5.12 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 1005 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2,3-dimethylbenzoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,3-dimethylbenzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,3-dimethyl-1-benzenecarbonyl isothiocyanate was prepared using the resultant 2,3-dimethyl-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml), and a solution of 2,3-dimethyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (81 mg, yield 98%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.31 (s, 6H), 3.95 (s, 3H), 3.96 (s, 3H), 6.42 (d, J=5.36 Hz, 1H), 7.19 (t, J=7.40 Hz, 1H), 7.29-7.34 (m, 4H), 7.41 (s, 1H), 7.48 (d, J=8.78 Hz, 1H), 7.53 (s, 1H), 7.44-7.78 (m, 1H), 8.22-8.24 (m, 1H), 1.1.82 (s, 1H), 12.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 1006 N-(2,4-Difluorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

2,4-Difluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-difluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2,4-Difluoro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (69 mg, yield 82%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.92 (s, 3H), 3.94 (s, 3H), 6.55 (d, J=5.12 Hz, 1H), 7.22-7.27 (m, 2H), 7.32 (d, J=9.08 Hz, 2H), 7.40-7.47 (m, 2H), 7.49 (s, 1H), 7.79-7.83 (m, 1H), 8.51 (d, J=5.12 Hz, 1H), 11.76 (s, 1H), 12.30 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 1007 N-(2,6-Difluorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

2,6-Difluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,6-difluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2,6-Difluoro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (62 mg, yield 74%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.94 (s, 3H), 6.44 (d, J=5.12 Hz, 1H), 6.84-6.87 (m, 1H), 7.02-7.25 (m, 4H), 7.37-7.49 (m, 2H), 7.59-7.63 (m, 2H), 7.80 (bs, 1H), 8.09 (bs, 1H), 8.45 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 1008 N-(2,4-Dichlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

2,4-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2,4-Dichloro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (70 mg, yield 78%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.05 (s, 3H), 4.06 (s, 3H), 6.57 (d, J=5.37 Hz, 1H), 7.26 (s, 1H), 7.35 (dd, J=2.19 Hz, J=8.42 Hz, 1H), 7.44-7.46 (m, 2H), 7.54-7.56 (m, 2H), 7.76-7.84 (m, 4H), 8.53 (d, J=5.37 Hz, 1H), 9.29 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 1009 N-(3,5-Dichlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

3,5-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3,5-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3,5-Dichloro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (73 mg, yield 79%).

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 1010 N-(3,4-Dimethoxybenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

3,5-Dimethoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3,5-dimethoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3,4-Dimethoxy-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (70 mg, yield 80%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.79 (s, 3H), 3.82 (s, 3H), 3.93 (s, 6H), 5.11 (bs, 1H), 6.37 (d, J=5.12 Hz, 1H), 6.66 (d, J=8.54 Hz, 2H), 6.91 (d, J=8.54 Hz, 2H), 7.03 (d, J=8.05 Hz, 1H), 7.35 (s, 1H), 7.43 (s, 1H), 7.49 (s, 1H), 7.55 (d, J=8.78 Hz, 1H), 8.29 (s, 1H), 8.41 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 520 (M⁺+1)

Example 1011 N-(2,4-Dichlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

2,4-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2,4-Dichloro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (78 mg, yield 90%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.11 (s, 3H), 4.17 (s, 3H), 6.79 (d, J=6.34 Hz, 1H), 7.21-7.17 (m, 1H), 7.26 (s, 1H), 7.34 (d, J=10.25 Hz, 1H), 7.45-7.47 (m, 2H), 7.57 (d, J=1.95 Hz, 1H), 7.60 (s, 1H), 7.79 (d, J=8.29 Hz, 1H), 7.83 (d, J=8.29 Hz, 1H), 8.54 (d, J=6.34 Hz, 1H), 9.44 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 547 (M⁺+1)

Example 1012 N-(2,6-Dichlorobenzoyl)-N′-[4-{(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

2,6-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,6-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2,6-Dichloro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (71 mg, yield 82%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.07 (s, 3H), 4.10 (s, 3H), 6.69 (d, J=5.86 Hz, 1H), 7.08-7.12 (m, 2H), 7.26-7.44 (m, 5H), 7.53 (s, 1H), 7.72 (bs, 1H), 8.55 (d, J=5.85 Hz, 1H), 8.89 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 547 (M⁺+1)

Example 1013 N-(2,4-Difluorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

2,4-Difluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-difluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2,4-Difluoro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (66 mg, yield 81%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.11 (s, 3H), 4.14 (s, 3H), 6.74 (d, J=5.86 Hz, 1H), 6.89-6.99 (m, 1H), 7.00-7.09 (m, 1H), 7.12-7.16 (m, 1H), 7.37-7.42 (m, 2H), 7.58 (d, J=7.56 Hz, 1H), 7.67 (s, 1H), 7.72 (s, 1H), 8.05-8.14 (m, 2H), 8.58 (d, J=6.10 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 514 (M⁺+1)

Example 1014 N-(2,4-Dichlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

2,4-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2,4-Dichloro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (64 mg, yield 74%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.14 (s, 3H), 4.18 (s, 3H), 6.91 (d, J=6.83 Hz, 1H), 7.36 (dd, J=2.07 Hz, 8.42 Hz, 1H), 7.42-7.46 (m, 4H), 7.56-7.65 (m, 2H), 7.72 (s, 1H), 7.86 (s, 1H), 8.21 (dd, J=2.44 Hz, J=11.71 Hz, 1H), 8.66 (d, J=6.59 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 547 (M⁺+1)

Example 1015 N-(3,5-Dichlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

3,5-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3,5-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3,5-Dichloro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (73 mg, yield 84%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.96 (s, 3H), 3.97 (s, 3H), 6.52 (d, J=5.12 Hz, 1H), 7.43 (s, 2H), 7.51-7.55 (m, 2H), 7.59 (m, 1H), 7.95 (s, 1H), 8.00 (s, 1H), 8.05-8.78 (m, 1H), 8.53 (d, J=5.37 Hz, 1H), 11.93 (bs, 1H), 12.42 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 547 (M⁺+1)

Example 1016 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2,4-dimethylbenzoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,4-dimethylbenzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,4-dimethyl-1-benzenecarbonyl isothiocyanate was prepared using the resultant 2,4-dimethyl-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 2,4-Dimethyl-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (75 mg, yield 97%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.34 (s, 3H), 2.42 (s, 3H), 3.95 (s, 3H), 3.96 (s, 3H), 6.42-6.44 (m, 1H), 7.10-7.13 (m, 2H), 7.41-7.53 (m, 5H), 7.73 (m, 1H), 8.22 (m, 1H), 8.50 (m, 1H), 11.96 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 5.23 (M⁺+1)

Example 1017 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2,5-dimethylbenzoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,5-dimethylbenzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,4-dimethyl-1-benzenecarbonyl isothiocyanate was prepared using the resultant 2,5-dimethyl-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 2,5-Dimethyl-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (74 mg, yield 94%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.33 (s, 3H), 2.39 (s, 3H), 3.97 (s, 3H), 3.98 (s, 3H), 6.48 (d, J=5.37 Hz, 1H), 7.14-7.27 (m, 2H), 7.35 (s, 1H), 7.43 (s, 1H), 7.50 (d, J=8.78 Hz, 1H), 7.56 (s, 1H), 7.76 (m, 1H), 8.22-8.24 (m, 1H), 8.55 (d, J=5.37 Hz, 1H), 11.77 (s, H), 12.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 1018 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2,3-dimethylbenzoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,3-dimethylbenzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,3-dimethyl-1-benzenecarbonyl isothiocyanate was prepared using the resultant 2,3-dimethyl-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 2,3-Dimethyl-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (76 mg, yield 96%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.29 (s, 6H), 3.94 (s, 3H), 3.96 (s, 3H), 6.57 (d, J=5.12 Hz, 1H), 7.20 (t, J=7.45 Hz, 1H), 7.30-7.34 (m, 4H), 7.41 (s, 1H), 7.51 (s, 1H), 7.85-7.87 (m, 3H), 8.53 (d, J=5.12 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 1019 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(3,5-dimethylbenzoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3,5-dimethylbenzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3,5-dimethyl-1-benzenecarbonyl isothiocyanate was prepared using the resultant 3,5-dimethyl-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 3,5-Dimethyl-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (77 mg, yield 97%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.36 (s, 6H), 3.94 (s, 3H), 3.96 (s, 3H), 6.62 (d, J=5.12 Hz, 1H), 7.31-7.32 (m, 2H), 7.41 (s, 1H), 7.52 (s, 1H), 7.64 (s, 2H), 7.84 (m, 2H), 8.53 (d, J=5.37 Hz, 1H), 11.47 (s, 1H), 12.67 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 1020 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2,6-difluorobenzoyl)thiourea

2,6-Difluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,6-difluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2,6-Difluoro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (59 mg, yield 74%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.94 (s, 3H), 3.96 (s, 3H), 6.57 (d, J=4.64 Hz, 1H), 7.11-7.51 (m, 4H), 7.62-7.64 (m, 1H), 7.80-7.83 (m, 2H), 8.08 (m, 1H), 8.52 (d, J=5.12 Hz, 1H), 12.16 (s, 1H), 12.28 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 530 (M⁺+1)

Example 1021 N-(2,4-Difluorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

2,4-Difluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-difluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2,4-Difluoro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (77 mg, yield 92%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.06 (s, 3H), 4.09 (s, 3H), 6.62 (d, J=5.61 Hz, 1H), 6.99-7.05 (m, 1H), 7.10-7.14 (m, 1H), 7.25-7.27 (m, 2H), 7.56 (s, 1H), 7.63 (s, 1H), 7.86 (d, J=8.78 Hz, 2H), 8.15-8.21 (m, 1H), 8.52 (d, J=5.61. Hz, 1H), 9.61 (d, J=14.64 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 497 (M⁺+1)

Example 1022 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-phenylacetyl)thiourea

2-Phenylethanoyl isothiocyanate was prepared using commercially available 2-phenylethanoyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Phenylethanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (64 mg, yield 80%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.82 (s, 2H), 3.96 (s, 3H), 3.98 (s, 3H), 6.51 (d, J=6.01 Hz, 1H), 7.25-7.35 (m, 7H), 7.44 (s, 1H), 7.48 (d, J=8.78 Hz, 1H), 7.51 (s, 1H), 7.69 (m, 1H), 8.14-8.16 (m, 1H), 8.57 (bs, 1H), 11.81 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 1023 N-(2-Cyclohexylacetyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

2-Cyclohexylethanoyl isothiocyanate was prepared using commercially available 2-cyclohexylethanoyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Cyclohexylethanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (73 mg, yield 90%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.86-1.00 (m, 2H), 1.19-1.25 (m, 6H), 1.69 (m, 3H), 2.37 (d, J=6.83 Hz, 2H), 3.96 (s, 3H), 3.99 (s, 3H), 6.67 (m, 1H), 7.34-7.36 (m, 2H), 7.44 (s, 1H), 7.59 (s, 1H), 7.81-7.84 (m, 2H), 8.63 (m, 1H), 11.48 (s, 1H), 12.41 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 1024 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(2-phenylacetyl)thiourea

2-Phenylethanoyl isothiocyanate was prepared using commercially available 2-phenylethanoyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Phenylethanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (65 mg, yield 83%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.83 (s, 2H), 3.92 (s, 3H), 3.95 (s, 3H), 6.64 (d, J=5.12 Hz, 1H), 7.13 (d, J=9.51 Hz, 1H), 7.29-7.36 (m, 6H), 7.41 (s, 1H), 7.46 (s, 1H), 8.05 (t, J=8.66 Hz, 1H), 8.55 (d, J=5.12 Hz, 1H), 11.89 (s, 1H), 12.26 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 1025 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[3-(2-methoxyphenyl)propanoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-(2-methoxyphenyl)propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-(2-methoxyphenyl)propanoyl isothiocyanate was prepared using the resultant 3-(2-methoxyphenyl)propanoyl chloride as a starting compound according to the description of the literature. 3-(2-Methoxyphenyl)propanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (60 mg, yield 74%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.71-2.75 (m, 2H), 2.85-2.89 (m, 2H), 3.81 (s, 3H), 3.94 (s, 3H), 3.96 (s, 3H), 6.55 (d, J=5.12 Hz, 1H), 6.87 (t, J=7.44 Hz, 1H), 6.95 (d, J=8.29 Hz, 1H), 7.16-7.22 (m, 2H), 7.28 (d, J=8.54 Hz, 2H), 7.39 (s, 1H), 7.49 (s, 1H), 7.76-7.79 (m, 2H), 8.50 (d, J=6.04 Hz, 1H), 11.49 (s, 1H), 12.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 518 (M⁺+1)

Example 1026 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(3-phenylpropanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-phenylpropanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-phenylpropanoyl isothiocyanate was prepared using the resultant 3-phenylpropanoyl chloride as a starting compound according to the description of the literature. 3-Phenylpropanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (60 mg, yield 74%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.81-2.91 (m, 2H), 2.99-3.03 (m, 2H), 4.07 (s, 3H), 4.09 (s, 3H), 6.76 (d, J=6.01 Hz, 1H), 7.06-7.11 (m, 2H), 7.21-7.32 (m, 3H), 7.56 (s, 3H), 7.73 (bs, 1H), 8.48 (m, 1H), 8.59 (d, J=5.86 Hz, 1H), 11.49 (s, 1H), 12.74 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 1027 N-(3-Cyclopentylpropanoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

3-Cyclopentylpropanoyl isothiocyanate was prepared using commercially available 3-cyclopentylpropanoyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Cyclopentylpropanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy)-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (63 mg, yield 80%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.13-1.25 (m, 4H), 1.50-1.61 (m, 7H), 1.75 (m, 2H), 3.92 (s, 3H), 3.95 (s, 3H), 6.60 (d, J=5.12 Hz, 1H), 7.34 (d, J=11.22 Hz, 1H), 7.28 (m, 1H), 7.32-7.35 (m, 1H), 7.41 (s, 1H), 7.45 (s, 1H), 8.11 (m, 1H), 8.53 (d, J=5.12 Hz, 1H), 11.63 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 498 (M⁺+1)

Example 1028 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(3-phenylpropanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-phenylpropanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-phenylpropanoyl isothiocyanate was prepared using the resultant 3-phenylpropanoyl chloride as a starting compound according to the description of the literature. 3-Phenylpropanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (57 mg, yield 71%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.79-2.84 (m, 2H), 2.89-2.94 (m, 2H), 4.02 (s, 3H), 4.03 (S, 3H), 6.88 (bs, 1H), 7.21-7.33 (m, 6H), 7.59-7.61 (m, 3H), 7.72 (s, 1H), 8.13 (d, J=13.17 Hz, 1H), 11.65 (s, 1H), 12.67 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 506 (M⁺+1)

Example 1029 N-(3-Cyclopentylpropanoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

3-Cyclopentylpropanoyl isothiocyanate was prepared using commercially available 3-cyclopentylpropanoyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Cyclopentylpropanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (69 mg, yield 88%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.11 (m, 2H), 1.49-1.62 (m, 7H), 1.75-1.91 (m, 4H), 3.95 (s, 3H), 3.96 (s, 3H), 6.52 (d, J=5.37 Hz, 1H), 7.43 (s, 1H), 7.47-7.56 (m, 3H), 8.05 (d, J=4.39 Hz, 1H), 8.52 (d, J=5.12 Hz, 1H), 11.58 (s, 1H), 12.66 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 498 (M⁺+1)

Example 1030 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(3-cyclopentylpropanoyl)thiourea

3-Cyclopentylpropanoyl isothiocyanate was prepared using commercially available 3-cyclopentylpropanoyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Cyclopentylpropanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (68 mg, yield 88%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.07 (m, 4H), 1.48-1.71 (m, 9H), 4.05 (s, 3H), 4.07 (s, 3H), 6.88 (d, J=6.83 Hz, 1H), 7.55 (s, 1H), 7.65 (d, J=9.03 Hz, 1H), 7.78-7.81 (m, 2H), 8.26-8.28 (m, 1H), 8.87 (d, J=6.59 Hz, 1H), 11.61 (s, 1H), 12.66 (s, 1H).

Mass spectrometry value (ESI-MS, m/z): 515 (M⁺+1)

Example 1031 N-[2-(Benzyloxy)acetyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl]thiourea

2-(Benzyloxy)ethanoyl isothiocyanate was prepared using commercially available 2-(benzyloxy)ethanoyl chloride (80 mg) as a starting compound according to the description of the literature. 2-(Benzyloxy)ethanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (38 mg, yield 43%).

Mass spectrometry value (ESI-MS, m/z): 522 (M⁺+1)

Example 1032 N-[2-(Benzyloxy)acetyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

2-(Benzyloxy)ethanoyl isothiocyanate was prepared using commercially available 2-(benzyloxy)ethanoyl chloride (80 mg) as a starting compound according to the description of the literature. 2-(Benzyloxy)ethanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (33 mg, yield 40%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.96 (s, 6H), 4.13 (s, 2H), 4.64 (s, 2H), 6.48 (d, J=5.37 Hz, 2H), 7.32-7.45 (m, 6H), 7.54 (m, 2H), 7.90-7.94 (m, 2H), 8.50 (d, J=5.12 Hz, 1H), 10.15 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 522 (M⁺+1)

Example 1033 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-furylcarbonyl)thiourea

2-Furancarbonyl isothiocyanate was prepared using commercially available 2-furancarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Furancarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (40 mg, yield 53%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.94 (s, 3H), 3.96 (s, 3H), 6.56 (d, J=5.12 Hz, 1H), 6.73-6.77 (m, 2H), 7.32 (d, J=8.78 Hz, 1H), 7.41 (s, 1H), 7.51-7.52 (m, 2H), 7.79 (d, J=8.78 Hz, 1H), 7.86 (m, 1H), 8.01 (s, 2H), 8.08 (s, 1H), 8.51 (d, J=4.88, 1H)

Mass spectrometry value (ESI-MS, m/z): 450 (M⁺+1)

Example 1034 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(3-thienylcarbonyl)thiourea

3-Thiophenecarbonyl isothiocyanate was prepared using commercially available 3-thiophenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Thiophenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (45 mg, yield 68%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.95 (s, 3H), 6.55 (d, J=5.37 Hz, 1H), 7.26 (t, J=4.27 Hz, 1H), 7.31 (d, J=9.03 Hz, 2H), 7.41 (s, 1H), 7.50 (s, 1H), 7.81 (d, J=9.03 Hz, 2H), 8.05 (d, J=4.88 Hz, 1H), 8.41 (d, J=3.90 Hz, 1H), 8.51 (d, J=5.12 Hz, 1H), 11.65 (s, 1H), 12.49 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 466 (M⁺+1)

Example 1035 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(2-furylcarbonyl)thiourea

2-Furancarbonyl isothiocyanate was prepared using commercially available 2-furancarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Furancarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (47 mg, yield 68%).

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 1036 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-(3-thienylcarbonyl)thiourea

3-Thiophenecarbonyl isothiocyanate was prepared using commercially available 3-thiophenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Thiophenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (45 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.96 (s, 3H), 6.67 (d, J=5.12 Hz, 1H), 7.15-7.18 (m, 1H), 7.26-7.28 (m, 2H), 7.39-7.43 (m, 2H), 7.48 (s, 1H), 7.99-8.08 (m, 2H), 8.42 (d, J=3.42 Hz, 1H), 8.57 (d, J=5.12 Hz, 1H), 10.01 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 484 (M⁺+1)

Example 1037 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-[(2,5-dimethyl-3-furyl)carbonyl]-thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,5-dimethyl-3-furoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,5-dimethyl-3-furancarbonyl isothiocyanate was prepared using the resultant 2,5-dimethyl-3-furancarbonyl chloride as a starting compound according to the description of the literature. 2,5-Dimethyl-3-furancarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (38 mg, yield 48%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.26 (s, 3H), 2.55 (s, 3H), 3.92 (s, 3H), 3.95 (s, 3H), 6.65 (d, J=5.37 Hz, 1H), 6.89 (s, 1H), 7.13-7.14 (m, 1H), 7.34-7.37 (m, 1H), 7.41 (s, 1H), 7.46 (s, 1H), 8.05-8.07 (m, 1H), 8.54 (d, J=5.15 Hz, 1H), 11.13 (s, 1H), 12.61 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 1038 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-[(3-methyl-2-thienyl)carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-methyl-2-thiophenecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-methyl-2-thiophenecarbonyl isothiocyanate was prepared using the resultant 3-methyl-2-thiophenecarbonyl chloride as a starting compound according to the description of the literature. 3-Methyl-2-thiophenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (42 mg, yield 53%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.51 (s, 3H), 3.92 (s, 3H), 3.96 (s, 3H), 6.66 (d, J=5.12 Hz, 1H), 7.09 (d, J=4.88 Hz, 1H), 7.14-7.16 (m, 1H), 7.38 (dd, J=2.56 Hz, 11.01 Hz, 1H), 7.42 (s, 1H), 7.46 (s, 1H), 7.86 (d, J=4.88 Hz, 1H), 8.07 (t, J=8.54 Hz, 1H), 8.55 (d, J=5.37 Hz, 1H), 11.25 (s, 1H), 12.22 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 498 (M⁺+1)

Example 1039 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-[(2,5-dimethyl-3-furyl)carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2,5-dimethyl-3-furoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2,5-dimethyl-3-furancarbonyl isothiocyanate was prepared using the resultant 2,5-dimethyl-3-furancarbonyl chloride as a starting compound according to the description of the literature. 2,5-Dimethyl-3-furancarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (51 mg, yield 64%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.26 (s, 3H), 2.55 (s, 3H), 3.96 (s, 6H), 6.51 (d, J=5.37 Hz, 1H), 6.87 (s, 1H), 7.42 (s, 1H), 7.47-7.59 (m, 3H), 8.07 (d, J=10.25 Hz, 1H), 8.51 (d, J=5.12 Hz, 1H), 11.02 (s, 1H), 12.81 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 1040 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-[(5-methyl-2-thienyl)carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 5-methyl-2-thiophenecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 5-methyl-2-thiophenecarbonyl isothiocyanate was prepared using the resultant 5-methyl-2-thiophenecarbonyl chloride as a starting compound according to the description of the literature. 5-Methyl-2-thiophenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (49 mg, yield 62%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.58 (s, 3H), 4.07 (s, 3H), 4.09 (s, 3H), 6.62 (d, J=5.61 Hz, 1H), 7.25-7.27 (m, 1H), 7.32-7.35 (m, 1H), 7.46-7.50 (m, 1H), 7.57-7.58 (m, 2H), 7.63 (s, 1H), 7.88-7.90 (m, 2H), 8.53 (d, J=5.61 Hz, 1H), 8.86 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 498 (M⁺+1)

Example 1041 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-{[(diethylamino)carbonyl]amino}methanethioamide

(Diethylamino)methanoyl isothiocyanate was prepared using commercially available N,N-diethylcarbamic chloride (80 mg) as a starting compound according to the description of the literature. (Diethylamino)methanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (42 mg, yield 55%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.26-1.29 (m, 6H), 3.93 (s, 3H), 3.95 (s, 3H), 4.22-4.24 (m, 4H), 6.54 (d, J=5.12 Hz, 1H), 7.11 (m, 2H), 7.29-7.31 (m, 2H), 7.41 (s, 1H), 7.50 (s, 1H), 7.73 (m, 2H), 8.52 (d, J=5.12 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 455 (M⁺+1)

Example 1042 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-[{[di(2-chloroethyl)amino]carbonyl}amino]methanethioamide

[Di(2-chloroethyl)amino]methanoyl isothiocyanate was prepared using commercially available N,N-di(2-chloroethyl)carbamic chloride (80 mg) as a starting compound according to the description of the literature. [Di(2-chloroethyl)amino]methanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (48 mg, yield 55%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.57-3.62 (m, 4H), 3.80-3.82 (m, 2H), 3.95 (s, 3H), 3.97 (s, 3H), 4.11-4.13 (m, 2H), 7.55 (m, 1H), 7.29-7.31 (m, 2H), 7.42 (s, 1H), 7.55 (s, 1H), 7.73-7.75 (m, 3H), 8.57 (d, J=5.37 Hz, 1H), 12.25 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 524 (M⁺+1)

Example 1043 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-{[(diisopropylamino)carbonyl]amino}methanethioamide

(Diisopropylamino)methanoyl isothiocyanate was prepared using commercially available N,N-diisopropylcarbamic chloride (80 mg) as a starting compound according to the description of the literature. (Diisopropylamino)methanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (50 mg, yield 62%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.19 (d, J=6.10 Hz, 2H), 1.27 (d, J=6.83 Hz, 12H), 3.94 (s, 3H), 3.96 (s, 3H), 6.39 (d, J=5.12 Hz, 1H), 7.42-7.46 (m, 4H), 7.53 (s, 2H), 7.64 (m, 1H), 8.13 (m, 1H), 8.49 (d, J=4.88 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 483 (M⁺+1)

Example 1044 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-tetrahydro-1H-1-pyrrolylcarbonylthiourea

1-Pyrrolidinecarbonyl isothiocyanate was prepared using commercially available 1-pyrrolidinecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 1-Pyrrolidinecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (48 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.85 (m, 8H), 3.92 (s, 3H), 3.94 (s, 3H), 6.52 (d, J=4.88 Hz, 1H), 7.27 (d, J=7.81 Hz, 2H), 7.39 (s, 1H), 7.49 (s, 1H), 7.75 (m, 2H), 8.49 (d, J=5.13 Hz, 1H), 9.59 (s, 1H), 12.80 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 453 (M⁺+1)

Example 1045 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-morpholinocarbonylthiourea

4-Morpholinecarbonyl isothiocyanate was prepared using commercially available 4-morpholinecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-Morpholinecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (49 mg, yield 62%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.53-3.55 (m, 4H), 3.74-3.78 (m, 4H), 4.05 (s, 3H), 4.07 (s, 3H), 6.58 (d, J=5.61 Hz, 1H), 7.21 (d, J=8.78 Hz, 2H), 7.26 (s, 1H), 7.54 (d, J=4.88 Hz, 2H), 7.76 (d, J=9.03 Hz, 2H), 7.98 (bs, 1H), 8.51 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 469 (M⁺+1)

Example 1046 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-{[(methylanilino)carbonyl]amino}methanethioamide

(Methylanilino)methanoyl isothiocyanate was prepared using commercially available N-methyl-N-phenylcarbamic chloride (80 mg) as a starting compound according to the description of the literature. (Methylanilino)methanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (52 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.57 (bs, 3H), 3.93 (s, 3H), 3.94 (s, 3H), 6.43 (d, J=5.37 Hz, 1H), 7.13-7.16 (m, 2H), 7.26-7.28 (m, 1H), 7.34-7.45 (m, 6H), 7.51 (s, 1H), 7.57 (d, J=9.03 Hz, 2H), 8.31 (s, 1H), 8.46 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 489 (M⁺+1)

Example 1047 N-[10,11-Dihydro-5H-dibenzo(b,f)-azepin-5-ylcarbonyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)-oxy]phenyl}thiourea

10,11-Dihydro-5H-dibenzo(b,f)azepine-5-carbonyl isothiocyanate was prepared using commercially available 10,11-dihydro-5H-dibenzo(b,f)azepine-5-carbonyl chloride (80 mg) as a starting compound according to the description of the literature. 10,11-Dihydro-5H-dibenzo(b,f)azepine-5-carbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (61 mg, yield 65%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.86 (m, 2H), 1.25 (m, 2H), 3.94 (s, 3H), 3.95 (s, 3H), 6.49 (d, J=5.37 Hz, 1H), 7.35-7.56 (m, 12H), 8.02 (m, 1H), 8.49-8.51 (m, 2H), 12.36 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 595 (M⁺+1)

Example 1048 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-{[(diethylamino)carbonyl]amino}-methanethioamide

(Diethylamino)methanoyl isothiocyanate was prepared using commercially available N,N-diethylcarbamic chloride (80 mg) as a starting compound according to the description of the literature. (Diethylamino)methanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (52 mg, yield 38%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.29 (t, J=7.19 Hz, 6H), 3.95 (s, 6H), 4.23-4.25 (m, 4H), 6.39 (d, J=5.12 Hz, 1H), 7.41 (s, 1H), 7.45 (d, J=8.78 Hz, 1H), 7.52 (s, 1H), 7.65 (m, 2H), 8.09 (m, 1H), 8.49 (d, J=5.61 Hz, 1H), 11.37 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 489 (M⁺+1)

Example 1049 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-[{[di(2-chloroethyl)amino]carbonyl}-amino]methanethioamide

[Di(2-chloroethyl)amino]methanoyl isothiocyanate was prepared using commercially available N,N-di(2-chloroethyl)carbamic chloride (80 mg) as a starting compound according to the description of the literature. [Di(2-chloroethyl)amino]methanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (51 mg, yield 60%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.55-3.63 (m, 4H), 3.81-3.84 (m, 2H), 3.95 (s, 6H), 4.11-4.15 (m, 2H), 6.41 (d, J=5.12 Hz, 1H), 7.40-7.44 (m, 3H), 7.52 (s, 1H), 7.61-7.63 (m, 1H), 8.09-8.12 (m, 1H), 8.49 (d, J=5.12 Hz, 1H), 12.29 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 558 (M⁺+1)

Example 1050 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-{[(diisopropylamino)carbonyl]-amino}methanethioamide

(Diisopropylamino)methanoyl isothiocyanate was prepared using commercially available N,N-diisopropylcarbamic chloride (80 mg) as a starting compound according to the description of the literature. (Diisopropylamino)methanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (49 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.18 (d, J=6.01 Hz, 2H), 1.27 (d, J=6.83 Hz, 12H), 3.93 (s, 3H), 3.95 (s, 3H), 6.53 (d, J=5.12 Hz, 1H), 7.28 (d, J=8.78 Hz, 2H), 7.41 (s, 1H), 7.50 (s, 1H), 7.73-7.75 (m, 3H), 8.51 (d, J=5.12 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 518 (M⁺+1)

Example 1051 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-tetrahydro-1H-1-pyrrolylcarbonylthiourea

1-Pyrrolidinecarbonyl isothiocyanate was prepared using commercially available 1-pyrrolidinecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 1-Pyrrolidinecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (52 mg, yield 70%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.85-1.99 (m, 8H), 3.95 (s, 6H), 6.41 (d, J=5.37 Hz, 1H), 7.42 (s, 1H), 7.46 (d, J=8.54 Hz, 1H), 7.53 (s, 1H), 7.64-7.66 (m, 2H), 8.17-8.19 (m, 2H), 8.50 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 487 (M⁺+1)

Example 1052 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-morpholinocarbonylthiourea

4-Morpholinecarbonyl isothiocyanate was prepared using commercially available 4-morpholinecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-Morpholinecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (40 mg, yield 52%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.53-3.56 (m, 4H), 3.75-3.77 (m, 4H), 4.08 (s, 3H), 4.10 (s, 3H), 5.77 (bs, 1H), 6.49 (d, J=5.61 Hz, 1H), 7.26-7.29 (m, 1H), 7.63 (s, 1H), 7.68-7.70 (m, 2H), 8.01 (s, 1H), 8.04 (d, J=2.44 Hz, 1H), 8.52 (d, J=5.85 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 503 (M⁺+1)

Example 1053 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-{[(methylanilino)carbonyl]amino}-methanethioamide

(Methylanilino)methanoyl isothiocyanate was prepared using commercially available N-methyl-N-phenylcarbamic chloride (80 mg) as a starting compound according to the description of the literature. (Methylanilino)methanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (56 mg, yield 71%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.57 (bs, 3H), 3.94 (s, 6H), 6.32 (d, J=5.12 Hz, 1H), 7.28-7.44 (m, 8H), 7.52-7.58 (m, 2H), 7.56 (s, 1H), 8.46-8.48 (m, 2H)

Mass spectrometry value (ESI-MS, m/z): 524 (M⁺+1)

Example 1054 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[10,11-dihydro-5H-dibenzo(b,f)-azepin-5-ylcarbonyl]thiourea

10,11-Dihydro-5H-dibenzo(b,f)azepine-5-carbonyl isothiocyanate was prepared using commercially available 10,11-dihydro-5H-dibenzo(b,f)-azepine-5-carbonyl chloride (80 mg) as a starting compound according to the description of the literature. 10,11-Dihydro-5H-dibenzo(b,f)azepine-5-carbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]-aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (46 mg, yield 50%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.86 (m, 2H), 1.25 (m, 2H), 3.94 (s, 3H), 3.95 (s, 3H), 6.39 (d, J=5.12 Hz, 1H), 7.35 (m, 6H), 7.41 (s, 1H), 7.45 (d, J=8.78 Hz, 1H), 7.51 (s, 1H), 7.56-7.57 (m, 2H), 7.68 (dd, J=2.44 Hz, 9.03 Hz, 1H), 8.14 (s, 1H), 8.49 (d, J=5.12 Hz, 1H), 8.53 (s, 1H), 12.29 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 612 (M⁺+1)

Example 1055 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[(2-phenylcyclopropyl)carbonyl]thiourea

2-Phenyl-1-cyclopropanecarbonyl isothiocyanate was prepared using commercially available 2-phenyl-1-cyclopropanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Phenyl-1-cyclopropanecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (53 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.09 (m, 1H), 1.52 (m, 2H), 1.59 (m, 2H), 3.94 (s, 3H), 3.96 (s, 3H), 6.59 (d, J=5.37 Hz, 1H), 7.19-7.32 (m, 5H), 7.41 (m, 2H), 7.52 (m, 2H), 7.78-7.80 (m, 3H), 8.54 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 500 (M⁺+1)

Example 1056 N-Cyclopropylcarbonyl-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

1-Cyclopropanecarbonyl isothiocyanate was prepared using commercially available 1-cyclopropanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 1-Cyclopropanecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (46 mg, yield 66%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.96-0.99 (m, 4H), 2.08-2.13 (m, 2H), 3.95 (s, 6H), 6.72 (d, J=5.12 Hz, 1H), 7.41 (s, 1H), 7.45-7.52 (m, 2H), 8.04 (d, J=11.95 Hz, 1H), 8.50 (d, J=5.12 Hz, 1H), 11.89 (s, 1H), 12.64 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 442 (M⁺+1)

Example 1057 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-[(2-phenylcyclopropyl)carbonyl]thiourea

2-Phenyl-1-cyclopropanecarbonyl isothiocyanate was prepared using commercially available 2-phenyl-1-cyclopropanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Phenyl-1-cyclopropanecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (51 mg, yield 62%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.08-1.25 (m, 1H), 1.53 (m, 2H), 1.59-1.62 (m, 2H), 3.95 (s, 6H), 6.49 (d, J=5.12 Hz, 1H), 7.19-7.55 (m, 8H), 8.05 (d, J=10.00 Hz, 1H), 8.50 (d, J=5.37 Hz, 1H), 11.88 (s, 1H), 12.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 518 (M⁺+1)

Example 1058 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-cyclopropylcarbonylthiourea

1-Cyclopropanecarbonyl isothiocyanate was prepared using commercially available 1-cyclopropanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 1-Cyclopropanecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (36 mg, yield 52%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.93-0.99 (m, 4H), 2.12 (m, 2H), 3.94 (s, 3H), 3.96 (s, 3H), 6.41 (d, J=5.37 Hz, 1H), 7.33 (d, J=11.95 Hz, 1H), 7.41 (s, 1H), 7.45 (d, J=8.78 Hz, 1H), 7.52 (s, 1H), 7.64-7.67 (m, 1H), 8.14 (s, 1H), 8.49 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 458 (M⁺+1)

Example 1059 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[(2-phenylcyclopropyl)carbonyl]-thiourea

2-Phenyl-1-cyclopropanecarbonyl isothiocyanate was prepared using commercially available 2-phenyl-1-cyclopropanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Phenyl-1-cyclopropanecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (48 mg, yield 60%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.09-1.11 (m, 1H), 1.53 (m, 2H), 1.60 (m, 2H), 3.94 (s, 3H), 3.96 (s, 3H), 6.40 (d, J=5.37 Hz, 1H), 7.16-7.34 (m, 5H), 7.41 (s, 1H), 7.45 (d, J=8.78 Hz, 1H), 7.52 (s, 1H), 7.67 (dd, J=2.32 Hz, 8.91 Hz, 1H), 8.14 (d, J=2.44 Hz, 1H), 8.49 (d, J=5.12 Hz, 1H), 11.88 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 535 (M⁺+1)

Example 1060 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[(2-phenylcyclopropyl)carbonyl]thiourea

2-Phenyl-1-cyclopropanecarbonyl isothiocyanate was prepared using commercially available 2-phenyl-1-cyclopropanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Phenyl-1-cyclopropanecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (50 mg, yield 60%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.93-0.97 (m, 1H), 1.31 (m, 1H), 1.52-1.60 (m, 2H), 3.98 (s, 6H), 6.55 (d, J=5.61 Hz, 1H), 7.18-7.33 (m, 5H), 7.45 (s, 1H), 7.56 (d, J=8.54 Hz, 1H), 7.59 (s, 1H), 7.69 (m, 1H), 8.17-8.19 (m, 1H), 8.60 (d, J=5.91 Hz, 1H), 11.88 (s, 1H), 12.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 501 (M⁺+1)

Example 1061 N-Cyclopentylcarbonyl-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

1-Cyclopentanecarbonyl isothiocyanate was prepared using commercially available 1-cyclopentanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 1-Cyclopentanecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (43 mg, yield 57%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.85-0.88 (m, 1H), 1.08-1.11 (m, 1H), 1.24 (bs, 1H), 1.57-1.91 (m, 6H), 3.93 (s, 3H), 3.95 (s, 3H), 6.54 (d, J=5.37 Hz, 1H), 7.19 (d, J=8.78 Hz, 1H), 7.29 (d, J=8.78 Hz, 2H), 7.39 (d, J=7.81 Hz, 1H), 7.50 (d, J=5.61 Hz, 1H), 7.73-7.78 (m, 3H), 8.51 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 452 (M⁺+1)

Example 1062 N-Cyclohexylcarbonyl-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

1-Cyclohexanecarbonyl isothiocyanate was prepared using commercially available 1-cyclohexanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 1-Cyclohexanecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (60 mg, yield 47%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.21-1.38 (m, 6H), 1.66-1.85 (m, 5H), 3.92 (s, 3H), 3.95 (s, 3H), 6.54 (d, J=5.12 Hz, 1H), 7.28 (d, J=9.03 Hz, 3H), 7.39 (s, 1H), 7.49 (s, 1H), 7.76 (d, J=8.78 Hz, 1H), 8.50 (d, J=5.12 Hz, 1H), 11.41 (bs, 1H), 12.56 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 466 (M⁺+1)

Example 1063 N-Cyclopentylcarbonyl-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

1-Cyclopentanecarbonyl isothiocyanate was prepared using commercially available 1-cyclopentanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 1-Cyclopentanecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (35 mg, yield 47%).

¹H-NMR (CDCl₃, 400 MHz): δ 0.879 (m, 1H), 1.08 (m, 1H), 1.17 (m, 1H), 1.63-1.97 (m, 6H), 4.07 (s, 3H), 4.09 (s, 3H), 6.86 (d, J=6.01 Hz, 1H), 7.16 (dd, J=9.52 Hz, 22.93 Hz, 1H), 7.63 (s, 1H), 7.69 (s, 2H), 8.56 (m, 1H), 8.68 (d, J=6.34 Hz, 1H), 11.47 (bs, 1H), 12.88 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 470 (M⁺+1)

Example 1064 N-Cyclohexylcarbonyl-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

1-Cyclohexanecarbonyl isothiocyanate was prepared using commercially available 1-cyclohexanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 1-Cyclohexanecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (47 mg, yield 61%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.21-1.39 (m, 6H), 1.66-1.90 (m, 5H), 3.92 (s, 3H), 3.95 (s, 3H), 6.64 (d, J=5.12 Hz, 1H), 7.12 (d, J=8.78 Hz, 1H), 7.35 (dd, J=2.55 Hz, 11.10 Hz, 1H), 7.41 (s, 1H), 7.45 (s, 1H), 8.09 (t, J=8.79 Hz, 1H), 8.53 (d, J=5.37 Hz, 1H), 11.57 (s, 1H), 12.42 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 484 (M⁺+1)

Example 1065 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(3-ethoxypropanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-ethoxypropanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-ethoxypropanoyl isothiocyanate was prepared using the resultant 3-ethoxypropanoyl chloride as a starting compound according to the description of the literature. 3-Ethoxypropanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (55 mg, yield 72%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.92-0.95 (m, 3H), 2.74 (m, 2H), 3.44-3.46 (m, 2H), 3.64-3.65 (m, 2H), 3.95 (s, 3H), 3.96 (s, 3H), 6.44 (d, J=5.37 Hz, 1H), 7.43 (s, 1H), 7.49 (d, J=8.78 Hz, 2H), 7.54 (s, 1H), 7.70 (m, 1H), 8.16 (m, 1H), 8.53 (d, J=5.12 Hz, 1H), 11.71 (s, 1H), 12.32 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 456 (M⁺+1)

Example 1066 N-(4-Chlorobutanoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

4-Chlorobutanoyl isothiocyanate was prepared using commercially available 4-chlorobutanoyl chloride (80 mg) as a starting compound according to the description of the literature. 4-Chlorobutanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (51 mg, yield 67%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.02-2.05 (m, 2H), 2.63-2.67 (m, 2H), 3.67-3.70 (m, 2H), 3.93 (s, 3H), 3.96 (s, 3H), 6.66 (d, J=5.37 Hz, 1H), 7.14 (d, J=6.59 Hz, 1H), 7.36-7.38 (m, 1H), 7.42 (s, 1H), 7.47 (s, 1H), 8.08 (t, J=8.78 Hz, 1H), 8.56 (d, J=5.37 Hz, 1H), 11.71 (s, 1H), 12.32 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 479 (M⁺+1)

Example 1067 N-{4-[(6,7-Dimethoxy-4-quinolyl)-oxy]-2-fluorophenyl}-N′-[3-(methylsulfanyl)propanoyl]-thiourea

3-(Methylsulfanyl)propanoyl isothiocyanate was prepared using commercially available 3-(methylsulfanyl)propanoyl chloride (80 mg) as a starting compound according to the description of the literature. 3-(Methylsulfanyl)propanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (43 mg, yield 57%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.74-2.76 (m, 2H), 2.79-2.81 (m, 2H), 3.17 (s, 3H), 3.92 (s, 3H), 3.96 (s, 3H), 6.65 (d, J=5.12 Hz, 1H), 7.14 (d, J=9.27 Hz, 1H), 7.35-7.38 (m, 1H), 7.42 (s, 1H), 7.46 (s, 1H), 8.08 (t, J=8.90 Hz, 1H), 8.55 (d, J=5.12 Hz, 1H), 11.71 (s, 1H), 12.34 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 476 (M⁺+1)

Example 1068 N-(4-Chlorobutanoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

4-Chlorobutanoyl isothiocyanate was prepared using commercially available 4-chlorobutanoyl chloride (80 mg) as a starting compound according to the description of the literature. 4-Chlorobutanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-3-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (41 mg, yield 54%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.02-2.06 (m, 2H), 2.63-2.67 (m, 2H), 3.68-3.71 (m, 2H), 3.97 (s, 3H), 3.98 (s, 3H), 6.63 (d, J=5.61 Hz, 1H), 7.44-7.59 (m, 6H), 8.07 (d, J=11.95 Hz, 1H), 8.59 (d, J=5.61 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 478 (M⁺+1)

Example 1069 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-[3-(methylsulfanyl)propanoyl]thiourea

3-(Methylsulfanyl)propanoyl isothiocyanate was prepared using commercially available 3-(methylsulfanyl)propanoyl chloride (80 mg) as a starting compound according to the description of the literature. 3-(Methylsulfanyl)propanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-3-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (38 mg, yield 50%).

¹H-NMR (DMSO-d₆, 400 MHz): 2.54 (s, 3H), 2.74-2.81 (m, 4H), 3.95 (s, 6H), 6.51 (d, J=5.12 Hz, 1H), 7.41 (s, 1H), 7.48-7.53 (m, 3H), 8.04 (d, J=10.49 Hz, H), 8.50 (d, J=5.12 Hz, 1H), 11.64 (s, 1H), 12.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 476 (M⁺+1)

Example 1070 N-(3,4-Dimethoxybenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

3,4-Dimethoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3,4-dimethoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3,4-dimethoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (54 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.79 (s, 3H), 3.81 (s, 3H), 3.96 (s, 3H), 5.47 (bs, 1H), 6.38 (bs, 1H), 6.44-6.47 (m, 1H), 6.54 (dd, J=2.52 Hz, J=14.79 Hz, 1H), 7.02-7.08 (m, 3H), 7.37 (s, 1H), 7.43 (s, 2H), 7.49 (s, 1H), 7.53-7.57 (m, 2H), 8.46 (d, J=5.12 Hz, 1H), 12.64 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 538 (M⁺+1)

Example 1071 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(3-ethoxypropanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-ethoxypropanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-ethoxypropanoyl isothiocyanate was prepared using the resultant 3-ethoxypropanoyl chloride as a starting compound according to the description of the literature. 3-Ethoxypropanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (46 mg, yield 62%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.06-1.13 (m, 3H), 2.72-2.75 (m, 2H), 3.44-3.47 (m, 2H), 3.64-3.67 (m, 2H), 3.95 (s, 3H), 3.97 (s, 3H), 6.63 (d, J=5.37 Hz, 1H), 7.29 (d, J=8.54 Hz, 2H), 7.44 (s, 1H), 7.56 (s, 1H), 7.78-7.82 (m, 2H), 8.59 (d, J=5.61 Hz, 1H), 11.51 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 490 (M⁺+1)

Example 1072 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-dodecanoylthiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available dodecanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and dodecanoyl isothiocyanate was prepared using the resultant dodecanoyl chloride as a starting compound according to the description of the literature. Dodecanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (58 mg, yield 60%).

¹H-NMR (CDCl₃, 400 MHz): δ 0.87-0.89 (m, 3H), 1.27 (m, 14H), 1.71-1.72 (m, 2H), 2.39-2.43 (m, 2H), 3.49 (s, 2H), 4.06 (s, 3H), 4.08 (s, 3H), 6.59 (d, J=5.61 Hz, 1H), 7.21-7.26 (m, 4H), 7.55 (s, 1H), 7.59 (s, 1H), 7.79 (d, J=8.98 Hz, 1H), 8.52 (d, J=5.61 Hz, 1H), 8.66 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 538 (M⁺+1)

Example 1073 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-tetradecanoylthiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available tetradecanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and tetradecanoyl isothiocyanate was prepared using the resultant tetradecanoyl chloride as a starting compound according to the description of the literature. Tetradecanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (58 mg, yield 60%).

¹H-NMR (CDCl₃, 400 MHz): δ 0.87-0.90 (m, 3H), 1.27 (m, 20H), 1.73 (m, 2H), 2.40-2.44 (m, 2H), 4.08 (s, 3H), 4.12 (s, 3H), 5.29 (s, 1H), 6.65 (d, J=6.09 Hz, 1H), 7.23-7.26 (m, 2H), 7.58 (s, 1H), 7.83-7.85 (m, 3H), 8.52 (d, J=6.09 Hz, 1H), 8.63 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 566 (M⁺+1)

Example 1074 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(2-methylhexanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-methylhexanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-methylhexanoyl isothiocyanate was prepared using the resultant 2-methylhexanoyl chloride as a starting compound according to the description of the literature. 2-Methylhexanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (54 mg, yield 68%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.86-0.89 (m, 4H), 1.10 (d, J=6.83 Hz, 3H), 1.27-1.32 (m, 5H), 2.74-2.76 (m, 1H), 3.94 (s, 3H), 3.96 (s, 3H), 6.58 (d, J=5.97 Hz, 1H), 7.31 (d, J=8.78 Hz, 2H), 7.42 (s, 1H), 7.52 (s, 1H), 7.78-7.82 (m, 3H), 8.55 (d, J=5.37 Hz, 1H), 11.50 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 468 (M⁺+1)

Example 1075 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-dodecanoylthiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available dodecanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and dodecanoyl isothiocyanate was prepared using the resultant dodecanoyl chloride as a starting compound according to the description of the literature. Dodecanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (60 mg, yield 68%).

¹H-NMR (CDCl₃, 400 MHz): δ 0.86-0.89 (m, 6H), 1.26-1.27 (m, 6H), 1.56-1.64 (m, 11H), 4.09 (s, 3H), 4.17 (s, 3H), 6.78 (d, J=6.34 Hz, 1H), 7.08-7.13 (m, 2H), 7.26 (s, 1H), 7.59 (s, 1H), 8.12 (bs, 1H), 8.56 (d, J=6.34 Hz, 1H), 8.62 (m, 1H), 8.79 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 556 (M⁺+1)

Example 1076 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}-N′-tetradecanoylthiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available tetradecanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and tetradecanoyl isothiocyanate was prepared using the resultant tetradecanoyl chloride as a starting compound according to the description of the literature. Tetradecanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (58 mg, yield 63%).

¹H-NMR (CDCl₃, 400 MHz): δ 0.86-0.89 (m, 3H), 1.27 (m, 18H), 2.49 (m, 2H), 2.58-2.59 (m, 4H), 4.11 (s, 3H), 4.17 (s, 3H), 6.38 (m, 1H), 7.08-7.11 (m, 2H), 7.35 (s, 3H), 7.61-7.63 (m, 2H), 8.17 (m, 1H)

Mass spectrometry value (ESI-MS, m/z): 584 (M⁺+1)

Example 1077 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-methylhexanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-methylhexanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-methylhexanoyl isothiocyanate was prepared using the resultant 2-methylhexanoyl chloride as a starting compound according to the description of the literature. 2-Methylhexanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (44 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.84-0.94 (m, 5H), 1.03-1.11 (m, 4H), 1.25-1.59 (m, 4H), 3.94 (s, 3H), 3.96 (s, 3H), 6.42 (d, J=5.37 Hz, 1H), 7.42 (s, 1H), 7.47 (d, J=8.78 Hz, 1H), 7.53 (s, 1H), 7.70-7.73 (m, 1H), 8.17-8.19 (m, 1H), 8.51 (d, J=5.12 Hz, 1H), 11.58 (s, 1H), 12.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 503 (M⁺+1)

Example 1078 N-(2-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}thiourea

Commercially available 2-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (68 mg, yield 85%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.18 (s, 3H), 2.35 (s, 3H), 4.07 (s, 6H), 6.35 (d, J=5.37 Hz, 1H), 7.07 (d, J=8.54 Hz, 1H), 7.26 (s, 1H), 7.44-7.49 (m, 2H), 7.52-7.57 (m, 3H), 7.61 (s, 1H), 7.68 (d, J=7.32 Hz, 1H), 8.48 (d, J=5.37 Hz, 1H), 9.41 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 1079 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(3-methylbenzoyl)thiourea

Commercially available 3-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (64 mg, yield 83%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.24 (s, 3H), 2.34 (s, 3H), 2.47 (s, 3H), 4.07 (s, 6H), 6.35 (d, J=5.37 Hz, 1H), 7.06 (d, J=8.54 Hz, 1H), 7.26 (s, 1H), 7.43-7.49 (m, 3H), 7.55 (d, J=8.78 Hz, 1H), 7.61 (s, 1H), 7.71-7.74 (m, 2H), 8.48 (d, J=5.12 Hz, 1H), 9.23 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 1080 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(4-methylbenzoyl)thiourea

Commercially available 4-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (60 mg, yield 78%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.18 (s, 3H), 2.33 (s, 3H), 2.47 (s, 3H), 4.07 (s, 6H), 6.35 (d, J=5.37 Hz, 1H), 7.26 (s, 2H), 7.37 (d, J=7.81 Hz, 2H), 7.44 (s, 1H), 7.54 (d, J=8.78 Hz, 1H), 7.61 (s, 1H), 7.83 (d, J=8.29 Hz, 2H), 8.48 (d, J=5.37 Hz, 1H), 9.22 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 1081 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(4-nitrobenzoyl)thiourea

Commercially available 4-nitro-1-benzenecarbonyl isothiocyanate (30 mg) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (62 mg, yield 75%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.42 (s, 3H), 2.34 (s, 3H), 4.07 (s, 6H), 6.35 (d, J=5.12 Hz, 1H), 7.07 (d, J=8.54 Hz, 1H), 7.27 (s, 2H), 7.44 (s, 1H), 7.52 (d, J=8.54 Hz, 1H), 7.61 (s, 1H), 8.17 (d, J=9.03 Hz, 2H), 8.42 (d, J=9.03 Hz, 2H), 8.48 (d, J=5.12 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 533 (M⁺+1)

Example 1082 N-(4-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}thiourea

Commercially available 4-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (55 mg, yield 68%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.19 (s, 3H), 2.33 (s, 3H), 4.06 (s, 6H), 6.35 (d, J=5.12 Hz, 1H), 7.06 (d, J=8.54 Hz, 1H), 7.26 (s, 1H), 7.44 (s, 1H), 7.51-7.56 (m, 3H), 7.61 (s, 1H), 7.89 (d, J=11.22 Hz, 2H), 8.48 (d, J=5.37 Hz, 1H), 9.22 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 1083 N-(3-Chlorobenzoyl)-N′-[4-1 (6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}thiourea

Commercially available 3-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (70 mg, yield 87%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.19 (s, 3H), 2.33 (s, 3H), 4.07 (s, 6H), 6.35 (d, J=5.37 Hz, 1H), 7.06 (d, J=8.54 Hz, 1H), 7.26 (s, 1H), 7.44 (s, 1H), 7.49-7.54 (m, 2H), 7.61 (s, 1H), 7.65 (d, J=9.03 Hz, 1H), 7.80 (d, J=10.49 Hz, 1H), 7.95 (s, 1H), 8.48 (d, J=5.12 Hz, 1H), 9.24 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 523 (M⁺+1)

Example 1084 N-Benzoyl-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}thiourea

Comercially available 1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (50 mg, yield 67%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.19 (s, 3H), 2.34 (s, 3H), 4.07 (s, 6H), 6.35 (d, J=5.37 Hz, 1H), 7.06 (d, J=8.54 Hz, 1H), 7.26 (s, 1H), 7.44 (s, 1H), 7.49-7.61 (m, 4H), 7.67-7.70 (m, 1H), 7.94 (d, J=8.54 Hz, 2H), 8.48 (d, J=5.37 Hz, 1H), 9.27 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 1085 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(2-methylbenzoyl)thiourea

Commercially available 2-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (61 mg, yield 79%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.19 (s, 3H), 2.35 (s, 3H), 2.59 (s, 3H), 4.07 (s, 6H), 6.35 (d, J=5.37 Hz, 1H), 7.07 (d, J=8.78 Hz, 1H), 7.26 (s, 1H), 7.33-7.36 (m, 2H), 7.45-7.49 (m, 2H), 7.55-7.61 (m, 3H), 8.48 (d, J=5.12 Hz, 1H), 8.96 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 1086 N-(2,4-Dichlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}thiourea

2,4-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2,4-Dichloro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (60 mg, yield 69%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.19 (s, 3H), 2.37 (s, 3H), 3.35 (s, 6H), 6.70 (d, J=6.59 Hz, 1H), 7.11 (d, J=8.54 Hz, 1H), 7.34 (dd, J=1.95, 8.29 Hz, 1H), 7.45-7.48 (m, 2H), 7.56-7.72 (m, 5H), 8.54 (d, J=6.31 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 557 (M⁺+1)

Example 1087 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(4-methoxybenzoyl)thiourea

4-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-Methoxy-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (55 mg, yield 69%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.09 (s, 3H), 2.22 (s, 3H), 3.86 (s, 3H), 3.95 (s, 6H), 6.29 (d, J=5.37 Hz, 1H), 7.06-7.12 (m, 3H), 7.40-7.46 (m, 2H), 7.57 (s, 1H), 8.05 (d, J=9.03 Hz, 2H), 8.47 (d, J=5.37 Hz, 1H), 11.47 (bs, 1H), 3.95 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 518 (M⁺+1)

Example 1088 N-(2,4-Difluorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}thiourea

2,4-Difluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-difluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2,4-Difluoro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (60 mg, yield 74%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.17 (s, 3H), 2.34 (s, 3H), 4.09 (s, 3H), 4.11 (s, 3H), 6.49 (d, J=6.59 Hz, 1H), 6.87-6.93 (m, 2H), 6.99-7.15 (m, 2H), 7.26-7.30 (m, 1H), 7.57-7.64 (m, 2H), 8.09-8.17 (m, 2H), 8.49 (d, J=6.58 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 524 (M⁺+1)

Example 1089 N-(4-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methylphenyl}thiourea

Commercially available 4-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (46 mg, yield 56%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.29 (s, 3H), 4.04 (s, 3H), 4.06 (s, 3H), 6.59 (d, J=5.37 Hz, 1H), 7.09-7.12 (m, 2H), 7.26 (s, 1H), 7.44 (s, 1H), 7.53-7.58 (m, 3H), 7.83-7.89 (m, 3H), 8.53 (d, J=5.37 Hz, 1H), 9.19 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 509 (M⁺+1)

Example 1090 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylphenyl}-N′-(2-methylbenzoyl)thiourea

Commercially available 2-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (46 mg, yield 59%).

¹H-NMR (CDCl₃₁ 400 MHz): δ 2.41 (s, 3H), 2.58 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.59 (d, J=5.37 Hz, 1H), 7.09-7.12 (m, 3H), 7.26 (s, 1H), 7.34-7.35 (m, 1H), 7.44 (s, 1H), 7.48 (t, J=7.56 Hz, 1H), 7.53 (s, 1H), 7.59 (d, J=7.81 Hz, 1H), 7.84 (d, J=8.54 Hz, 1H), 8.53 (d, J=5.12 Hz, 1H), 8.95 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 1091 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylphenyl}-N′-(3-fluorobenzoyl)thiourea

3-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Fluoro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (64 mg, yield 81%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.39 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.59 (d, J=5.37 Hz, 1H), 7.09-7.12 (m, 2H), 7.26 (s, 1H), 7.36-7.41 (m, 1H), 7.44 (s, 1H), 7.53-7.59 (m, 2H), 7.66-7.71 (m, 2H), 7.84 (d, J=8.29 Hz, 1H), 8.54 (d, J=5.12 Hz, 1H), 9.19 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 1092 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylphenyl}-N′-(4-nitrobenzoyl)thiourea

Commercially available 4-nitro-1-benzenecarbonyl isothiocyanate (30 mg) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (41 mg, yield 49%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.39 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.59 (d, J=5.37 Hz, 1H), 7.11-7.13 (m, 2H), 7.26 (s, 2H), 7.44 (s, 1H), 7.52 (s, 1H), 7.83 (d, J=8.54 Hz, 1H), 8.13 (d, J=9.03 Hz, 2H), 8.42 (d, J=8.78 Hz, 2H), 8.54 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 519 (M⁺+1)

Example 1093 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylphenyl}-N′-(4-fluorobenzoyl)thiourea

4-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-Fluoro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (35 mg, yield 44%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.39 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.59 (d, J=5.37 Hz, 1H), 7.09-7.12 (m, 2H), 7.23-7.28 (m, 3H), 7.44 (s, 1H), 7.53 (s, 1H), 7.84 (d, J=8.29 Hz, 1H), 7.96-7.99 (m, 2H), 8.53 (d, J=5.37 Hz, 1H), 9.19 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 1094 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylphenyl}-N′-(2-fluorobenzoyl)thiourea

2-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Fluoro-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (41 mg, yield 52%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.39 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.59 (d, J=5.37 Hz, 1H), 7.09-7.12 (m, 2H), 7.24-7.29 (m, 3H), 7.39 (t, J=7.68 Hz, 1H), 7.44 (s, 1H), 7.53 (s, 1H), 7.64-7.69 (m, 1H), 7.86 (d, J=8.29 Hz, 1H), 8.12-8.16 (m, 1H), 8.53 (d, J=5.12 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 492 (M⁺+1)

Example 1095 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylphenyl}-N′-(4-methoxybenzoyl)thiourea

4-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-Methoxy-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (37 mg, yield 45%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.40 (s, 3H), 3.92 (s, 6H), 4.05 (s, 3H), 7.03-7.11 (m, 4H), 7.26 (s, 5H), 7.56 (s, 1H), 7.90-7.92 (m, 3H)

Mass spectrometry value (ESI-MS, m/z): 504 (M⁺+1)

Example 1096 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylphenyl}-N′-(4-methylbenzoyl)thiourea

Commercially available 4-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (44 mg, yield 56%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.39 (s, 3H), 2.47 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.59 (d, J=5.37 Hz, 1H), 7.08-7.12 (m, 2H), 7.26 (s, 1H), 7.36 (d, J=7.81 Hz, 2H), 7.44 (s, 1H), 7.53 (s, 1H), 7.81-7.86 (m, 3H), 8.53 (d, J=5.12 Hz, 1H), 9.19 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 1097 N-(2-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methylphenyl}thiourea

Commercially available 2-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (47 mg, yield 57%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.41 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.59 (d, J=5.12 Hz, 1H), 7.09-7.12 (m, 2H), 7.26 (s, 2H), 7.44-7.48 (m, 2H), 7.53-7.54 (m, 2H), 7.82 (d, J=7.08 Hz, 1H), 7.88 (d, J=8.54 Hz, 1H), 8.54 (d, J=5.12 Hz, 1H), 9.38 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 1098 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylphenyl}-N′-(3-methylbenzoyl)thiourea

Commercially available 3-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (32 mg, yield 40%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.39 (s, 3H), 2.47 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.59 (d, J=5.37 Hz, 1H), 7.09-7.12 (m, 2H), 7.26 (s, 1H), 7.44-7.49 (m, 3H), 7.53 (s, 1H), 7.71-7.74 (m, 2H), 7.87 (d, J=8.29 Hz, 1H), 8.53 (d, J=5.37 Hz, 1H), 9.21 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 1099 N-Benzoyl-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methylphenyl}thiourea

Commercially available 1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (44 mg, yield 58%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.39 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.59 (d, J=5.37 Hz, 1H), 7.09-7.12 (m, 3H), 7.25 (s, 1H), 7.44 (s, 1H), 7.53 (s, 1H), 7.58 (t, J=7.08 Hz, 2H), 7.68 (t, J=7.32 Hz, 1H), 7.86 (d, J=8.29 Hz, 2H), 7.94 (d, J=8.54 Hz, 1H), 9.23 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 1100 N-(3-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methylphenyl}thiourea

Commercially available 3-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (41 mg, yield 50%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.39 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.59 (d, J=5.12 Hz, 1H), 7.09-7.12 (m, 2H), 7.27 (s, 1H), 7.44 (s, 1H), 7.49-7.54 (m, 2H), 7.65 (d, J=8.05 Hz, 1H), 7.79 (d, J=8.29 Hz, 1H), 7.85 (d, J=8.54 Hz, 1H), 7.95 (s, 1H), 8.53 (d, J=5.37 Hz, 1H), 9.19 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 1101 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-methylbenzoyl)thiourea

Commercially available 2-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (40 mg, yield 52%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.64 (s, 3H), 3.92 (s, 3H), 3.93 (s, 3H), 6.60 (d, J=5.12 Hz, 1H), 7.19-7.21 (m, 2H), 7.34 (m, 2H), 7.41-7.47 (m, 3H), 7.52 (m, 2H), 8.16-8.20 (m, 1H), 8.52-8.53 (m, 2H)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 1102 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(4-methylbenzoyl)thiourea

Commercially available 4-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (38 mg, yield 49%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.41 (s, 3H), 3.94 (s, 3H), 3.97 (s, 3H), 6.69 (d, J=5.37 Hz, 1H), 7.33-7.37 (m, 4H), 7.44 (s, 1H), 7.54 (s, 1H), 7.60 (d, J=2.68 Hz, 1H), 7.94 (d, J=8.29 Hz, 1H), 8.14 (d, J=9.03 Hz, 1H), 8.59 (d, J=5.37 Hz, 1H), 11.74 (s, 1H), 12.75 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 509 (M⁺+1)

Example 1103 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-methoxybenzoyl)thiourea

2-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Methoxy-1-benzenecarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (36 mg, yield 45%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 4.04 (s, 3H), 6.42 (d, J=5.12 Hz, 1H), 7.18 (t, J=7.69 Hz, 1H), 7.30 (d, J=8.54 Hz, 1H), 7.41 (s, 1H), 7.48 (d, J=8.76 Hz, 1H), 7.52 (s, 1H), 7.68 (t, J=6.96 Hz, 1H), 7.76 (dd, J=2.56, 8.90 Hz, 1H), 7.94 (d, J=7.81 Hz, 1H), 8.20 (d, J=2.44 Hz, 1H), 8.49 (d, J=5.12 Hz, 1H), 11.29 (s, 1H), 12.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 1104 N-(2-Chlorobenzoyl)-N′-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

Commercially available 2-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (38 mg, yield 48%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 4.05 (s, 3H), 6.67 (d, J=5.12 Hz, 1H), 7.20 (d, J=7.81 Hz, 1H), 7.32-7.36 (m, 2H), 7.43 (s, 1H), 7.47 (s, 1H), 7.54-7.66 (m, 2H), 7.67 (d, J=6.59 Hz, 1H), 8.13 (d, J=8.78 Hz, 1H), 8.58 (d, J=5.12 Hz, 1H), 12.23 (s, 1H), 12.36 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 1105 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(2-phenylacetyl)thiourea

2-Phenylethanoyl isothiocyanate was prepared using commercially available 2-phenylethanoyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-phenylethanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (44 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.08 (s, 3H), 2.15 (s, 3H), 3.85 (s, 2H), 3.94 (s, 3H), 3.95 (s, 3H), 6.28 (d, J=5.12 Hz, 1H), 7.08 (d, J=8.54 Hz, 1H), 7.27-7.41 (m, 7H), 7.57 (s, 1H), 8.47 (d, J=5.37 Hz, 1H), 11.75 (bs, 1H), 12.01 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 1106 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(3-cyclopentylpropanoyl)thiourea

3-Cyclopentylpropanoyl isothiocyanate was prepared using commercially available 3-cyclopentylpropanoyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Cyclopentylpropanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (32 mg, yield 41%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.11 (m, 2H), 1.49-1.61 (m, 7H), 1.63-1.79 (m, 4H), 3.92 (s, 3H), 3.93 (s, 3H), 6.65 (d, J=5.37 Hz, 1H), 7.31 (d, J=11.71 Hz, 1H), 7.47 (s, 1H), 7.48 (s, 1H), 7.58 (d, J=2.68 Hz, 1H), 8.12 (d, J=8.78 Hz, 1H), 8.56 (d, J=6.83 Hz, 1H), 11.67 (s, 1H), 12.53 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 515 (M⁺+1)

Example 1107 N-Benzoyl-N′-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

Commercially available 1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (36 mg, yield 48%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.92 (s, 3H), 3.96 (s, 3H), 6.66 (d, J=5.37 Hz, 1H), 7.32 (d, J=8.78 Hz, 1H), 7.42 (s, 1H), 7.48 (s, 1H), 7.53-7.57 (m, 3H), 7.66-7.68 (m, 1H), 8.02 (d, J=8.54 Hz, 2H), 8.13 (d, J=9.03 Hz, 1H), 8.56 (d, J=5.37 Hz, 1H), 11.38 (s, 1H), 12.70 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 495 (M⁺+1)

Example 1108 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-N′-(4-nitrobenzoyl)thiourea

Commercially available 4-nitro-1-benzenecarbonyl isothiocyanate (30 mg) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (79 mg, yield 94%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.17 (s, 3H), 3.96 (s, 6H), 6.36 (d, J=5.12 Hz, 1H), 7.41 (s, 1H), 7.57 (s, 2H), 7.72 (bs, 2H), 8.19 (d, J=8.78 Hz, 2H), 8.29 (s, 1H), 8.36 (d, J=8.54 Hz, 2H), 8.48 (d, J=5.12 Hz, 2H)

Mass spectrometry value (ESI-MS, m/z): 519 (M⁺+1)

Example 1109 N-Benzoyl-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-methylphenyl}thiourea

Commercially available 1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (61 mg, yield 80%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.24 (s, 3H), 4.09 (s, 3H), 4.12 (s, 3H), 6.58 (d, J=6.09 Hz, 1H), 7.26 (s, 1H), 7.56-7.81 (m, 8H), 7.93 (d, J=7.32 Hz, 2H), 8.49 (d, J=5.86 Hz, 1H), 9.14 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 1110 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylphenyl}-N′-(3-methylbenzoyl)thiourea

Commercially available 3-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (65 mg, yield 83%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.17 (s, 3H), 2.41 (s, 3H), 3.96 (s, 6H), 6.37 (d, J=4.88 Hz, 1H), 7.33 (d, J=9.02 Hz, 1H), 7.41-7.48 (m, 4H), 7.56 (s, 1H), 7.72-7.85 (m, 3H), 8.48 (d, J=5.37 Hz, 1H), 11.53 (s, 1H), 12.67 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 1111 N-(4-Chlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-methylphenyl}thiourea

Commercially available 4-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-methylaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (52 mg, yield 64%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.24 (s, 3H), 4.08 (s, 3H), 4.09 (s, 3H), 6.44 (d, J=5.37 Hz, 1H), 7.17 (d, J=8.54 Hz, 1H), 7.26 (s, 1H), 7.55 (d, J=8.29 Hz, 3H), 7.62 (d, J=7.81 Hz, 3H), 7.71 (d, J=7.81 Hz, 1H), 7.87 (d, J=8.54 Hz, 1H), 8.49 (d, J=5.61 Hz, 1H), 9.11 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 1112 N-(2,6-Dichlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

2,6-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,6-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,6-dichloro-1-benzenecarbonyl in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (55 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.52 (d, J=5.12 Hz, 1H), 7.38-7.79 (m, 7H), 8.07-8.10 (m, 1H), 8.52 (d, J=5.12 Hz, 1H), 12.30 (bs, 1H), 12.43 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 547 (M⁺+1)

Example 1113 N-(2,4-Dimethoxybenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

2,4-Dimethoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-dimethoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,4-dimethoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (45 mg, yield 53%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.87 (s, 3H), 3.90 (s, 3H), 3.96 (s, 3H), 4.06 (s, 3H), 6.52 (d, J=6.34 Hz, 1H), 6.79-6.81 (m, 2H), 7.43 (s, 2H), 7.50-7.55 (m, 1H), 7.64 (d, J=11.22 Hz, 1H), 7.99 (d, J=9.03 Hz, 1H), 8.11 (d, J=14.64 Hz, 1H), 8.52 (d, J=5.12 Hz, 1H), 11.09 (bs, 1H), 12.76 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 538 (M⁺+1)

Example 1114 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2,4-dichlorobenzoyl)thiourea

2,4-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,4-dichloro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (53 mg, yield 62%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.43 (d, J=5.12 Hz, 1H), 7.43-8.17 (m, 7H), 8.17 (bs, 1H), 8.52 (d, J=5.12 Hz, 1H), 12.13 (bs, 1H), 12.28 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 563 (M⁺+1)

Example 1115 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2,6-dichlorobenzoyl)thiourea

2,6-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,6-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,6-dichloro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (40 mg, yield 47%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.43 (d, J=5.37 Hz, 1H), 7.43 (s, 1H), 7.47-7.61 (m, 5H), 7.77-7.98 (m, 1H), 8.18-8.20 (m, 1H), 8.52 (d, J=5.12 Hz, 1H), 12.24 (bs, 1H), 12.43 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 563 (M⁺+1)

Example 1116 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(3,5-dichlorobenzoyl)thiourea

3,5-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3,5-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3,5-dichloro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (55 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.42 (d, J=4.64 Hz, 1H), 7.42 (s, 1H), 7.49 (d, J=8.78 Hz, 1H), 7.53 (s, 1H), 7.72-8.00 (m, 6H), 8.16 (bs, 1H), 8.50 (d, J=5.12 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 563 (M⁺+1)

Example 1117 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2,4-dimethoxybenzoyl)thiourea

2,4-Dimethoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-dimethoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,4-dimethoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (53 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.90 (s, 3H), 3.95 (s, 3H), 3.96 (s, 3H), 4.06 (s, 3H), 6.43 (d, J=5.12 Hz, 1H), 6.73-6.81 (m, 2H), 7.43 (s, 1H), 7.49-7.53 (m, 3H), 7.78 (dd, J=2.44 Hz, J=8.78 Hz, 1H), 8.12 (bs, 1H), 8.51 (d, J=5.12 Hz, 1H), 11.09 (bs, 1H), 12.69 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 555 (M⁺+1)

Example 1118 N-(2,6-Dichlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

2,6-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,6-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,6-dichloro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (57 mg, yield 64%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 4.09 (s, 3H), 4.13 (s, 3H), 6.69 (d, J=6.09 Hz, 1H), 7.11-7.44 (m, 6H), 7.62 (s, 1H), 7.79-7.98 (m, 3H), 8.52 (d, J=6.34 Hz, 1H), 8.81 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 1119 N-(2,4-Dimethoxybenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

2,4-Dimethoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-dimethoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,4-dimethoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (42 mg, yield 48%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.90 (s, 3H), 3.93 (s, 3H), 3.95 (s, 3H), 4.06 (s, 3H), 6.56 (d, J=5.37 Hz, 1H), 6.79-6.81 (m, 2H), 7.33 (d, J=9.03 Hz, 2H), 7.41 (s, 1H), 7.50 (s, 1H), 7.84 (d, J=8.78 Hz, 2H), 8.01 (d, J=9.03 Hz, 1H), 8.52 (d, J=5.12 Hz, 1H), 11.05 (bs, 1H), 12.67 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 520 (M⁺+1)

Example 1120 N-(3,4-Dichlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

3,4-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3,4-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3,4-dichloro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (56 mg, yield 63%).

¹H-NMR (CDCl₃, 400 MHz): δ 4.05 (s, 3H), 4.06 (s, 3H), 6.62 (d, J=5.37 Hz, 1H), 7.24 (s, 1H), 7.26 (s, 1H), 7.61-7.68 (m, 6H), 7.73 (m, 1H), 7.81 (d, J=9.03 Hz, 1H), 8.04 (d, J=1.95 Hz, 1H), 8.54 (d, J=5.12 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 1121 N-(2,4-Difluorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

2,4-Difluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-difluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,4-difluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (56 mg, yield 68%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.96 (s, 3H), 6.66 (d, J=5.12 Hz, 1H), 7.13-7.84 (m, 7H), 8.04 (m, 1H), 8.56 (d, J=5.12 Hz, 1H), 11.95 (s, 1H), 12.18 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 514 (M⁺+1)

Example 1122 N-(3,5-Dichlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

3,5-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3,5-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3,5-dichloro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (51 mg, yield 64%).

Mass spectrometry value (ESI-MS, m/z): 547 (M⁺+1)

Example 1123 N-(2,4-Dimethoxybenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

2,4-Dimethoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-dimethoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,4-dimethoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (54 mg, yield 67%).

Mass spectrometry value (ESI-MS, m/z): 538 (M⁺+1)

Example 1124 N-(4-Cyclohexylbenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-cyclohexylbenzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-cyclohexyl-1-benzenecarbonyl isothiocyanate was prepared using the resultant 4-cyclohexyl-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-cyclohexyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (44 mg, yield 48%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.31-1.83 (m, 11H), 3.93 (s, 3H), 3.95 (s, 3H), 6.56 (d, J=5.12 Hz, 1H), 7.31 (d, J=8.54 Hz, 3H), 7.39 (d, J=6.83 Hz, 4H), 7.49 (s, 1H), 7.83 (m, 3H), 7.95 (d, J=8.05 Hz, 3H), 8.50 (d, J=5.12 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 542 (M⁺+1)

Example 1125 N-(4-Phenylbenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-fluorophenyl}thiourea

4-Phenyl-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-phenyl-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-phenyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (41 mg, yield 47%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.96 (s, 3H), 6.67 (d, J=5.12 Hz, 1H), 7.19 (m, 1H), 7.43-7.53 (m, 7H), 7.78 (d, J=7.81 Hz, 2H), 7.86 (d, J=8.19 Hz, 2H), 8.11-8.13 (m, 2H), 8.56 (d, J=5.37 Hz, 1H), 11.87 (s, 1H), 12.57 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 554 (M⁺+1)

Example 1126 N-(1,3-Benzodioxol-5-ylcarbonyl)-N′-{3-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

1,3-Benzodioxole-5-carbonyl isothiocyanate was prepared using commercially available 1,3-benzodioxole-5-carbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 1,3-benzodioxole-5-carbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (47 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.18 (s, 2H), 6.42 (d, J=5.12 Hz, 1H), 7.08 (d, J=8.48 Hz, 1H), 7.43 (s, 1H), 7.50 (d, J=8.78 Hz, 1H), 7.54 (s, 1H), 7.57 (s, 1H), 7.67 (d, J=8.29 Hz, 1H), 7.74 (d, J=9.03 Hz, 1H), 8.19 (bs, 1H), 8.51 (d, J=5.12 Hz, 1H), 11.49 (bs, 1H), 12.67 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 538 (M⁺+1)

Example 1127 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(4-cyclohexylbenzoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-cyclohexylbenzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-cyclohexyl-1-benzenecarbonyl isothiocyanate was prepared using the resultant 4-cyclohexyl-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-cyclohexyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (47 mg, yield 54%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.31-1.83 (m, 11H), 3.95 (s, 6H), 6.41 (d, J=4.88 Hz, 1H), 7.39 (d, J=9.27 Hz, 4H), 7.47 (d, J=8.54 Hz, 1H), 7.73 (m, 1H), 7.95 (d, J=7.56 Hz, 2H), 8.21 (m, 1H), 8.49 (d, J=5.61 Hz, 1H), 11.54 (s, 1H), 12.74 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 577 (M⁺+1)

Example 1128 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(4-octylbenzoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-octylbenzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-octyl-1-benzenecarbonyl isothiocyanate was prepared using the resultant 4-octyl-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-octyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (47 mg, yield 54%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.83-0.88 (m, 4H), 1.25-1.28 (m, 7H), 1.58-1.60 (m, 3H), 2.60-2.69 (m, 3H), 3.91 (s, 3H), 3.96 (s, 3H), 6.57 (d, J=5.12 Hz, 1H), 7.25 (d, J=8.05 Hz, 1H), 7.32-7.42 (m, 4H), 7.51 (s, 1H), 7.58 (s, 1H), 7.78 (d, J=8.05 Hz, 1H), 7.84-7.86 (m, 2H), 7.94 (d, J=8.05 Hz, 2H), 8.53 (d, J=5.37 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 572 (M⁺+1)

Example 1129 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(3,5-dimethylbenzoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) was added to commercially available 3,5-dimethylbenzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3,5-dimethyl-1-benzenecarbonyl isothiocyanate was prepared using the resultant 3,5-dimethyl-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3,5-dimethyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (39 mg, yield 47%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.37 (s, 6H), 3.95 (s, 3H), 3.96 (s, 3H), 6.41 (d, J=5.37 Hz, 1H), 7.29 (s, 1H), 7.41 (s, 1H), 7.47 (d, J=8.78 Hz, 1H), 7.53 (s, 1H), 7.63 (s, 2H), 7.71-7.74 (m, 2H), 8.19-8.20 (m, 1H), 8.50 (d, J=5.37 Hz, 1H), 11.54 (s, 1H), 12.72 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 1130 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(1,2,3,4-tetrahydro-2-isoquinolylcarbonyl)-thiourea

Commercially available 1,2,3,4-tetrahydroisoquinoline (50 mg) was dissolved in chloroform (10 ml), and triphosgene (111 mg) was added to the solution. The mixture was stirred at room temperature for 2 hr. The solvent was removed by distillation to give 1,2,3,4-tetrahydro-2-isoquinolinecarbonyl chloride. 1,2,3,4-Tetrahydro-2-isoquinolinecarbonyl isothiocyanate was prepared using this compound as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 1,2,3,4-tetrahydro-2-isoquinolinecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (78 mg, yield 94%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.81-2.89 (m, 4H), 3.92 (s, 3H), 3.94 (s, 3H), 4.87 (m, 2H), 6.52 (d, J=5.12 Hz, 1H), 7.13-7.28 (m, 4H), 7.39-7.49 (m, 4H), 7.73 (d, J=8.29 Hz, 2H), 8.49 (d, J=5.12 Hz, 1H), 10.18 (bs, 1H), 12.51 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 515 (M⁺+1)

Example 1131 N-(3-Cyclopentylpropanoyl)-N′-{4-[6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

3-Cyclopentylpropanoyl isothiocyanate was prepared using commercially available 3-cyclopentylpropanoyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-cyclopentylpropanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (46 mg, yield 57%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.11 (m, 1H), 1.50-1.76 (m, 8H), 2.32-2.33 (m, 2H), 2.67-2.68 (m, 2H), 3.95 (s, 3H), 3.98 (s, 3H), 6.51 (d, J=4.39 Hz, 1H), 6.79 (d, J=2.68 Hz, 1H), 7.39-7.52 (m, 4H), 8.04 (d, J=12.20 Hz, 1H), 8.52 (d, J=5.37 Hz, 1H), 11.58 (bs, 1H), 12.65 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 1132 N-(3-Cyclopentylpropanoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

3-Cyclopentylpropanoyl isothiocyanate was prepared using commercially available 3-cyclopentylpropanoyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-cyclopentylpropanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (37 mg, yield 46%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.28-1.32 (m, 1H), 1.48-1.63 (m, 5H), 1.73-1.79 (m, 3H), 2.32-2.33 (m, 2H), 2.67-2.68 (m, 2H), 3.98 (s, 3H), 3.99 (s, 3H), 7.34-7.39 (m, 3H), 7.58 (s, 2H), 7.71-7.75 (m, 2H), 8.57 (s, 2H), 11.48 (bs, 1H), 12.54 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 1133 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[3-(2-methylphenyl)propanoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-(2-methylphenyl)-propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-(2-methylphenyl)propanoyl isothiocyanate was prepared using the resultant 3-(2-methylphenyl)propanoyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-(2-methylphenyl)propanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (48 mg, yield 57%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.32 (s, 3H), 2.59-2.63 (m, 2H), 2.89-2.94 (m, 2H), 3.93 (s, 3H), 3.99 (s, 3H), 7.09-7.24 (m, 7H), 7.38 (s, 1H), 7.55 (s, 1H), 7.67 (d, J=8.78 Hz, 2H); 8.53 (s, 1H), 10.03 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 503 (M⁺+1)

Example 1134 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-[3-(2-methylphenyl)propanoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-(2-methylphenyl)-propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-(2-methylphenyl)propanoyl isothiocyanate was prepared using the resultant 3-(2-methylphenyl)propanoyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-(2-methylphenyl)propanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (45 mg, yield 54%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.33 (s, 3H), 2.75-2.79 (m, 2H), 2.87-2.91 (m, 2H), 3.95 (s, 3H), 3.96 (s, 3H), 6.51 (d, J=5.12 Hz, 1H), 7.11-7.16 (m, 5H), 7.42 (s, 1H), 7.48-7.57 (m, 2H), 8.04 (d, J=14.63 Hz, 1H), 8.51 (d, J=5.37 Hz, 1H), 11.64 (s, 1H), 12.62 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 520 (M⁺+1)

Example 1135 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[3-(methylsulphenyl)propanoyl]thiourea

3-(Methylsulphenyl)propanoyl isothiocyanate was prepared using commercially available 3-(methylsulphenyl)propanoyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-(methylsulphenyl)propanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (41 mg, yield 56%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.05 (s, 3H), 2.73-2.82 (m, 4H), 4.02 (s, 3H), 4.04 (s, 3H), 6.84 (m, 1H), 7.35 (d, J=7.32 Hz, 1H), 7.45 (d, J=7.32 Hz, 1H), 7.53 (s, 1H), 7.73 (s, 1H), 7.86-7.90 (m, 4H), 8.79 (d, J=5.13 Hz, 1H)

Mass spectrometry value (ESI-MS, m/z): 458 (M⁺+1)

Example 1136 N-[4-(Chloromethyl)benzoyl]-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

4-(Chloromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-(chloromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-(chloromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (54 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.98 (s, 3H), 4.00 (s, 3H), 4.44 (s, 2H), 6.72 (d, J=5.86 Hz, 1H), 7.40 (d, J=8.54 Hz, 2H), 7.47 (s, 1H), 7.58-7.63 (m, 3H), 7.88-7.89 (m, 2H), 8.03 (d, J=8.29 Hz, 2H), 8.67 (d, J=5.61 Hz, 1H), 11.68 (bs, 1H), 12.62 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 1137 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[4-(chloromethyl)benzoyl]thiourea

4-(Chloromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-(chloromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]-aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-(chloromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (52 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.99 (s, 3H), 4.00 (s, 3H), 4.45 (s, 2H), 6.62 (d, J=5.85 Hz, 1H), 7.48 (s, 1H), 7.57-7.65 (m, 4H), 7.82 (m, 1H), 8.03 (d, J=7.47 Hz, 2H), 8.25 (m, 1H), 8.66 (d, J=5.86 Hz, 1H), 11.77 (bs, 1H), 12.62 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 543 (M⁺+1)

Example 1138 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[2-(2-methylphenoxy)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-methylphenoxy)-acetic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-methylphenoxy)ethanoyl isothiocyanate was prepared using the resultant 2-(2-methylphenoxy)ethanoyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-(2-methylphenoxy)ethanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (37 mg, yield 44%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.22 (s, 3H), 3.96 (s, 3H), 3.98 (s, 3H), 4.44 (s, 2H), 6.62 (d, J=8.78 Hz, 2H), 6.80-6.93 (m, 5H), 7.11-7.16 (m, 2H), 7.35 (s, 1H), 7.39 (bs, 1H), 7.52 (s, 1H), 8.51 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 505 (M⁺+1)

Example 1139 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(4-phenylbutanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-phenylbutanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-phenylbutanoyl isothiocyanate was prepared using the resultant 4-phenylbutanoyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-phenylbutanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (37 mg, yield 45%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.85-1.93 (m, 3H), 2.59-2.68 (m, 3H), 3.98 (s, 3H), 3.99 (s, 3H), 6.76 (d, J=8.78 Hz, 1H), 7.19-7.36 (m, 6H), 7.39 (s, 1H), 7.57 (s, 1H), 7.73 (d, J=8.78 Hz, 2H), 8.57 (s, 1H), 11.49 (s, 1H), 12.51 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 503 (M⁺+1)

Example 1140 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N-ethyl-N′-(4-phenylbutanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-phenylbutanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-phenylbutanoyl isothiocyanate was prepared using the resultant 4-phenylbutanoyl chloride as a starting compound according to the description of the literature. N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-N-ethylamine (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-phenylbutanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (45 mg, yield 56%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.15-1.19 (m, 3H), 1.52 (m, 2H), 2.04-2.09 (m, 2H), 2.21-2.33 (m, 2H), 3.85 (s, 3H), 3.94 (s, 3H), 4.21 (bs, 1H), 6.40 (d, J=5.12 Hz, 1H), 7.08-7.40 (m, 12H), 8.33 (d, J=4.88 Hz, 1H), 10.48 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 530 (M⁺+1)

Example 1141 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[3-(2-methoxyphenyl)propanoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-(2-methoxyphenyl)propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-(2-methoxyphenyl)propanoyl isothiocyanate was prepared using the resultant 4-phenylbutanoyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-(2-methoxyphenyl)propanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (37 mg, yield 43%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.73-2.77 (m, 2H), 2.85-2.89 (m, 2H), 3.92 (s, 3H), 3.98 (s, 3H), 3.99 (s, 3H), 6.87-6.91 (m, 2H), 6.97 (d, J=8.29 Hz, 1H), 7.17-7.23 (m, 1H), 7.36 (d, J=8.78 Hz, 2H), 7.39 (s, 1H), 7.57 (s, 1H), 7.73 (d, J=8.78 Hz, 2H), 8.57 (s, 1H), 11.51 (bs, 1H), 12.52 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 519 (M⁺+1)

Example 1142 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-ethyl-N′-[3-(2-methoxyphenyl)propanoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-(2-methoxyphenyl)propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-(2-methoxyphenyl)propanoyl isothiocyanate was prepared using the resultant 4-phenylbutanoyl chloride as a starting compound according to the description of the literature. N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-N-ethylamine (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-(2-methoxyphenyl)propanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (44 mg, yield 52%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.19-1.18 (m, 3H), 2.32 (m, 2H), 2.52-2.54 (m, 2H), 3.72 (s, 3H), 3.93 (s, 3H), 3.97 (s, 3H), 6.51 (d, J=5.37 Hz, 1H), 6.82-6.85 (m, 1H), 6.91 (d, J=7.56 Hz, 1H), 6.95-6.99 (m, 1H), 7.00-7.19 (m, 7H), 7.42 (s, 1H), 7.53 (s, 1H), 8.42 (bs, 1H), 10.49 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 546 (M⁺+1)

Example 1143 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-ethyl-N′-[(2-phenylcyclopropyl)carbonyl]thiourea

2-Phenyl-1-cyclopropanecarbonyl isothiocyanate was prepared using commercially available 2-phenyl-1-cyclopropanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-N-ethylamine (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-phenyl-1-cyclopropanecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (43 mg, yield 53%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.60-1.19 (m, 3H), 1.23 (m, 2H), 1.91 (m, 2H), 1.91 (bs, 2H), 3.91 (s, 3H), 3.95 (s, 3H), 4.21 (m, 2H), 6.46 (d, J=5.12 Hz, 1H), 7.03 (d, J=7.56 Hz, 2H), 7.15-7.33 (m, 5H), 7.42 (s, 1H), 7.50 (s, 1H), 8.45 (d, J=5.37 Hz, 1H), 10.78 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 528 (M⁺+1)

Example 1144 N-[2-(2-Chlorophenoxy)propanoyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-chlorophenoxy)-propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-chlorophenoxy)propanoyl isothiocyanate was prepared using the resultant 2-(2-chlorophenoxy)propanoyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-(2-chlorophenoxy)propanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (45 mg, yield 50%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.61 (d, J=6.59 Hz, 3H), 3.93 (s, 3H), 3.98 (s, 3H), 5.21-5.22 (m, 1H), 6.99-7.05 (m, 2H), 7.32-7.35 (m, 3H), 7.38 (s, 1H), 7.47 (d, J=8.05 Hz, 1H), 7.70-7.74 (m, 3H), 8.55 (s, 1H), 11.65 (bs, 1H), 12.09 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 540 (M⁺+1)

Example 1145 N-(1,3-Benzodioxol-5-ylcarbonyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}thiourea

1,3-Benzodioxole-5-carbonyl isothiocyanate was prepared using commercially available 1,3-benzodioxole-5-carbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 1,3-benzodioxole-5-carbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (62 mg, yield 75%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.18 (s, 2H), 6.52 (d, J=4.88 Hz, 1H), 7.09 (d, J=8.30 Hz, 1H), 7.43 (s, 1H), 7.49-7.61 (m, 4H), 7.67 (d, J=1.87 Hz, J=7.29 Hz, 1H), 8.08 (d, J=11.22 Hz, 1H), 8.52 (d, J=5.16 Hz, 1H), 11.49 (bs, 1H), 12.72 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 522 (M⁺+1)

Example 1146 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[(5-methyl-2-thienyl)carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 5-methyl-2-thiophenecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 5-methyl-2-thiophenecarbonyl isothiocyanate was prepared using the resultant 5-methyl-2-thiophenecarbonyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 5-methyl-2-thiophenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (42 mg, yield 52%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.51 (s, 3H), 4.01 (s, 6H), 6.78-6.82 (m, 1H), 6.96 (s, 1H), 6.99 (s, 1H), 7.53-7.65 (m, 3H), 7.91 (d, J=3.42 Hz, 1H), 8.14 (d, J=10.98 Hz, 1H), 8.24 (d, J=3.42 Hz, 1H), 8.71 (d, J=5.86 Hz, 1H), 11.66 (bs, 1H), 12.62 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 1147 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-phenylacetyl)thiourea

2-Phenylethanoyl isothiocyanate was prepared using commercially available 2-phenylethanoyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-phenylethanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (41 mg, yield 53%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.88 (s, 2H), 3.94 (s, 3H), 3.96 (s, 3H), 6.41 (d, J=5.12 Hz, 1H), 7.29-7.36 (m, 5H), 7.42 (s, 1H), 7.46 (d, J=8.78 Hz, 1H), 7.52 (s, 1H), 7.66-7.69 (m, 1H), 8.11-8.14 (m, 1H), 8.51 (d, J=5.12 Hz, 1H), 11.82 (s, 1H), 12.44 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 1148 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-phenylacetyl)thiourea

2-Phenylethanoyl isothiocyanate was prepared using commercially available 2-phenylethanoyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-phenylethanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (38 mg, yield 48%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.66 (s, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 7.23-7.34 (m, 10H), 7.55 (s, 1H), 7.69 (d, J=9.03 Hz, 1H), 8.53 (s, 1H), 10.28 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 475 (M⁺+1)

Example 1149 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N-ethyl-N′-(2-phenylacetyl)thiourea

2-Phenylethanoyl isothiocyanate was prepared using commercially available 2-phenylethanoyl chloride (80 mg) as a starting compound according to the description of the literature. N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-N-ethylamine (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-phenylethanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (38 mg, yield 48%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.13-1.19 (m, 3H), 3.44 (bs, 2H), 3.94 (s, 3H), 3.96 (s, 3H), 4.19 (bs, 2H), 6.55 (d, J=5.37 Hz, 1H), 7.06-7.11 (m, 3H), 7.19-7.34 (m, 6H), 7.42 (s, 1H), 7.47 (s, 1H), 8.53 (d, J=5.12 Hz, 1H), 10.74 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 1150 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-2-morpholinoaniline

3-Fluoro4-nitrophenol (300 mg), morpholine (800 μl), and calcium carbonate (50 mg) were added to dimethylformamide (3 ml), and the mixture was heated at 130° C. for 12 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give 3-morpholino-4-nitrophenol (400 mg, yield 94%). The resultant 3-morpholino-4-nitrophenol (400 mg) was added to dimethylformamide (3 ml). Palladium hydroxid-carbon (110 mg) and hydrogen were added thereto, and the mixture was stirred at room temperature for 4 hr. The reaction solution was filtered through Celite, and the filtrate was concentrated. The residue was then purified by chromatography on silica gel using chloroform/acetone for development to give 4-amino-3-morpholinophenol (296 mg, yield 85%). The resultant 4-amino-3-morpholinophenol (296 mg), 4-chloro-6,7-dimethoxyquinazoline (479 mg), and n-tetraethylammonium bromide (244 mg) were dissolved in ethyl methyl ketone (10 ml) to prepare a solution. A solution (10 ml) of sodium hydroxide (479 mg) in water was added to the solution, and the mixture was sitrred at 80° C. for 4 hr. Water was added to the reaction solution, and the organic layer was extracted and was concentrated. The residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (396 mg, yield 68%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.59-3.61 (m, 4H), 3.76-3.81 (m, 4H), 3.92 (s, 3H), 3.93 (s, 3H), 7.16 (s, 2H), 7.23 (s, 2H), 8.52 (s, 2H)

Mass spectrometry value (ESI-MS, m/z): 383 (M⁺+1)

Example 1151 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-morpholinophenyl}-N′-(2-methylbenzoyl)thiourea

N-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenyl}-2-morpholinoaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 2-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (65 mg, yield 89%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.50 (s, 3H), 2.88-2.91 (m, 4H), 3.79-3.81 (m, 4H), 3.98 (s, 3H), 3.99 (s, 3H), 7.14 (d, J=11.22 Hz, 1H), 7.18 (s, 1H), 7.33 (d, J=9.76 Hz, 2H), 7.40 (s, 1H), 7.45 (t, J=7.40 Hz, 1H), 7.54 (d, J=7.56 Hz, 1H), 7.57 (s, 1H), 7.59 (s, 1H), 8.67 (d, J=12.93 Hz, 1H), 11.76 (s, 1H), 13.09 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 560 (M⁺+1)

Example 1152 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-(3-pyridylcarbonyl)thiourea

3-Pyridinecarbonyl isothiocyanate was prepared using commercially available 3-pyridinecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-pyridinecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (83 mg, yield 64%).

¹H-NMR (CDCl₃, 400 MHz): δ 3.95 (s, 3H), 4.06 (s, 3H), 6.57 (d, J=5.12 Hz, 1H), 7.24-7.27 (m, 3H), 7.45 (s, 1H), 7.51-7.54 (m, 2H), 7.82 (d, J=6.83 Hz, 2H), 8.21-8.24 (m, 1H), 8.53 (d, J=5.12 Hz, 1H), 8.89-8.91 (m, 1H), 9.18 (d, J=2.44 Hz, 1H), 9.22 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 461 (M⁺+1)

Example 1153 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[4-(morpholinomethyl)benzoyl]thiourea

Commercially available 4-bromomethylbenzoic acid (300 mg) was dissolved in acetonitrile (10 ml). Potassium carbonate (30 mg) and morpholine (130 μl) were added to the solution, and the mixture was stirred at room temperature for one hr. The reaction layer was subjected to separation with chloroform and a saturated aqueous sodium hydrogencarbonate solution. The organic layer was then concentrated to give methyl 4-(morpholinomethyl)benzoate. Methanol (1 ml), water (150 μl), and potassium hydroxide (15 mg) were added to the residue, and the mixture was heated at 60° C. for one hr. After the completion of the reaction, the solvent was removed by distillation to give 4-(morpholinomethyl)benzoic acid. Toluene (20 ml) and thionyl chloride (1 ml) were added to the residule, and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-(morpholinomethyl)-1-benzenecarbonyl isothiocyanate was prepared using the resultant 4-(morpholinomethyl)-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-(morpholinomethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (74 mg, yield 78%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.47 (s, 4H), 3.59 (s, 2H), 3.72-3.75 (m, 4H), 4.07 (s, 3H), 4.08 (s, 3H), 7.27 (s, 2H), 7.32-7.34 (m, 3H), 7.53-7.56 (m, 3H), 7.85-7.88 (m, 4H), 8.64 (s, 1H), 9.12 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 559 (M⁺+1)

Example 1154 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[(6-methyl-3-pyridyl)carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 6-methylnicotinic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 6-methyl-3-pyridinecarbonyl isothiocyanate was prepared using the resultant 6-methyl-3-pyridinecarbonyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 6-methyl-3-pyridinecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (71 mg, yield 89%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.58 (s, 3H), 3.97 (s, 3H), 3.99 (s, 3H), 7.37-7.40 (m, 3H), 7.46 (d, J=8.29 Hz, 1H), 7.58 (s, 1H), 7.79 (d, J=8.78 Hz, 2H), 8.26 (dd, J=2.44 Hz, J=8.05 Hz, 1H), 8.59 (s, 1H), 9.00 (d, J=2.19 Hz, 1H), 11.82 (bs, 1H), 12.52 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 476 (M⁺+1)

Example 1155 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(4-pyridylcarbonyl)thiourea

4-Pyridinecarbonyl isothiocyanate was prepared using commercially available 4-pyridinecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-pyridinecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (73 mg, yield 94%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.98 (s, 3H), 3.99 (s, 3H), 7.37-7.40 (m, 3H), 7.58 (s, 1H), 7.79 (d, J=8.78 Hz, 2H), 7.87 (d, J=6.09 Hz, 2H), 8.58 (s, 1H), 8.79 (d, J=6.09 Hz, 2H), 11.89 (bs, 1H), 12.34 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 462 (M⁺+1)

Example 1156 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-pyridylcarbonyl)thiourea

2-Pyridinecarbonyl isothiocyanate was prepared using commercially available 2-pyridinecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-pyridinecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (69 mg, yield 90%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.98 (s, 3H), 3.99 (s, 3H), 7.39-7.42 (m, 3H), 7.58 (s, 1H), 7.81-7.84 (m, 3H), 8.16-8.20 (m, 1H), 8.28 (d, J=7.56 Hz, 1H), 8.58 (s, 1H), 8.82 (d, J=4.64 Hz, 1H), 10.85 (bs, 1H), 12.18 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 462 (M⁺+1)

Example 1157 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[2-(trifluoromethyl)benzoyl]thiourea

2-(Trifluoromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-(trifluoromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-(trifluoromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (49 mg, yield 56%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.99 (s, 3H), 4.02 (s, 3H), 7.38-7.40 (m, 2H), 7.59 (s, 1H), 7.76-7.88 (m, 7H), 8.58 (s, 1H), 12.14 (bs, 1H), 12.29 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 1158 N-(3,5-Dichlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

3,5-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3,5-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3,5-dichloro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (40 mg, yield 45%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.98 (s, 3H), 3.99 (s, 3H), 7.37-7.40 (m, 4H), 7.58 (s, 1H), 7.67 (bs, 1H), 7.76-7.81 (m, 1H), 7.88 (s, 1H), 7.94 (s, 1H), 8.00 (s, 1H), 8.17 (bs, 1H), 8.58 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 530 (M⁺+1)

Example 1159 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(3,5-dichlorobenzoyl)thiourea

3,5-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3,5-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3,5-dichloro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (40 mg, yield 47%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.96 (s, 3H), 6.66 (d, J=4.88 Hz, 1H), 7.43 (s, 1H), 7.48 (s, 1H), 7.61 (s, 1H), 7.67 (s, 1H), 7.79 (s, 1H), 7.94-8.17 (m, 3H), 8.57 (d, J=5.12 Hz, 1H), 12.09 (bs, 1H), 12.42 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 563 (M⁺+1)

Example 1160 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluorophenyl}-N′-(2-fluorobenzoyl)thiourea

2-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (68 mg, yield 86%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.52 (d, J=4.88 Hz, 1H), 7.35-7.40 (m, 2H), 7.43 (s, 1H), 7.50-7.55 (m, 2H), 7.61-7.73 (m, 2H), 7.75 (t, J=5.85 Hz, 1H), 8.07 (d, J=11.95 Hz, 1H), 8.52 (d, J=5.37 Hz, 1H), 11.85 (s, 1H), 12.43 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 496 (M⁺+1)

Example 1161 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-fluorobenzoyl)thiourea

2-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-fluoro-1-benzenecarbonyl isothiocyanate (50 μl) in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (43 mg, yield 53%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.98 (s, 3H), 3.99 (s, 3H), 7.34-7.40 (m, 5H), 7.58 (s, 1H), 7.60-7.79 (m, 4H), 8.58 (s, 1H), 11.74 (s, 1H), 12.32 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 479 (M⁺+1)

Example 1162 N-(2,6-Dichlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

2,6-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,6-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,6-dichloro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (56 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.98 (s, 3H), 3.99 (s, 3H), 7.39 (d, J=10.73 Hz, 3H), 7.47-7.61 (m, 4H), 7.79 (d, J=8.78 Hz, 2H), 8.59 (s, 1H), 12.22 (bs, 1H), 12.35 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 530 (M⁺+1)

Example 1163 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(3-fluorobenzoyl)thiourea

3-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (50 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.92 (s, 3H), 3.93 (s, 3H), 6.66 (d, J=5.12 Hz, 1H), 7.20 (s, 1H), 7.32-7.36 (m, 1H), 7.43 (s, 1H), 7.48 (s, 1H), 7.60-7.62 (m, 2H), 7.86 (d, J=9.03 Hz, 1H), 8.56 (d, J=5.12 Hz, 1H), 11.95 (bs, 1H), 12.55 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 512 (M⁺+1)

Example 1164 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(3-fluorobenzoyl)thiourea

3-Fluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-fluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-fluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (60 mg, yield 75%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.98 (s, 3H), 3.99 (s, 3H), 7.37-7.40 (m, 3H), 7.52-7.55 (m, 1H), 7.58-7.61 (m, 2H), 7.78-7.86 (m, 4H), 8.58 (s, 1H), 12.05 (bs, 1H), 12.43 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 479 (M⁺+1)

Example 1165 N-(3-Bromobenzoyl)-N′-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

3-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (56 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.46 (s, 3H), 3.92 (s, 3H), 6.61 (d, J=5.37 Hz, 1H), 7.19-7.22 (m, 1H), 7.32-7.36 (m, 1H), 7.48 (s, 1H), 7.52 (t, J=7.93 Hz, 1H), 7.61 (d, J=2.68 Hz, 1H), 7.88 (d, J=8.05 Hz, 1H), 7.99 (d, J=8.05 Hz, 1H), 8.09 (d, J=9.06 Hz, 1H), 8.21 (s, 1H), 8.56 (d, J=5.12 Hz, 1H), 12.02 (bs, 1H), 12.53 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 573 (M⁺+1)

Example 1166 N-(4-Bromobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

4-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (57 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.96 (s, 3H), 6.55 (d, J=5.12 Hz, 1H), 7.33 (d, J=8.78 Hz, 2H), 7.41 (s, 1H), 7.51 (s, 1H), 7.77 (d, J=8.78 Hz, 2H), 7.82 (d, J=8.78 Hz, 2H), 7.93 (d, J=8.54 Hz, 2H), 8.52 (d, J=5.37 Hz, 1H), 11.65 (bs, 1H), 12.47 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 539 (M⁺+1)

Example 1167 N-(4-Bromobenzoyl)-N′-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

4-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (46 mg, yield 53%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.92 (s, 3H), 3.93 (s, 3H), 6.66 (d, J=5.12 Hz, 1H), 7.20 (s, 1H), 7.32-7.36 (m, 1H), 7.43 (s, 1H), 7.48 (s, 1H), 7.60 (d, J=2.68 Hz, 1H), 7.78 (d, J=8.78 Hz, 1H), 7.95 (d, J=8.78 Hz, 1H), 8.56 (d, J=5.12 Hz, 1H), 11.96 (bs, 1H), 12.57 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 573 (M⁺+1)

Example 1168 N-(4-Bromobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

4-Bromo-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-bromo-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-bromo-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (53 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.98 (s, 3H), 3.99 (s, 3H), 7.37-7.40 (m, 3H), 7.58 (s, 1H), 7.76-7.92 (m, 4H), 7.94 (d, J=6.59 Hz, 2H), 8.58 (s, 1H), 11.72 (bs, 1H), 12.52 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 541 (M⁺+1)

Example 1169 N-{2-[4-(Bromomethyl)phenyl]acetyl}-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-(bromomethyl)benzoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-[4-(bromomethyl)phenyl]ethanoyl isothiocyanate was prepared using the resultant 4-(bromomethyl)-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-[4-(bromomethyl)phenyl]-ethanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (50 mg, yield 52%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.85 (s, 2H), 3.92 (s, 3H), 3.95 (s, 3H), 4.36 (s, 2H), 6.55 (d, J=5.12 Hz, 1H), 7.29 (d, J=9.03 Hz, 2H), 7.30-7.41 (m, 5H), 7.49 (s, 1H), 7.75 (d, J=8.78 Hz, 2H), 8.29 (d, J=5.37 Hz, 1H), 11.75 (bs, 1H), 12.39 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 567 (M⁺+1)

Example 1170 N-(5-Chloropentanoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

5-Chloropentanoyl isothiocyanate was prepared using commercially available 5-chloropentanoyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 5-chloropentanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (46 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.49-2.55 (m, 6H), 3.36-3.69 (m, 2H), 3.93 (s, 3H), 3.96 (s, 3H), 7.34-7.39 (m, 3H), 7.58 (s, 1H), 7.73 (d, J=9.03 Hz, 2H), 8.58 (s, 1H), 11.49 (s, 1H), 12.50 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 475 (M⁺+1)

Example 1171 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-phenyl}-N′-[2-(2-thienyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-thienyl)acetic acid (40 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-thienyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-thienyl)ethanoyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-(2-thienyl)ethanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (44 mg, yield 54%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.96 (s, 3H), 3.98 (s, 3H), 4.07 (s, 2H), 6.64 (d, J=5.61 Hz, 1H), 6.96-7.03 (m, 6H), 7.33-7.38 (m, 1H), 7.45 (s, 1H), 7.78 (d, J=9.03 Hz, 1H), 8.61 (d, J=5.37 Hz, 1H), 11.75 (bs, 1H), 12.34 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 480 (M⁺+1)

Example 1172 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[2-(2-thienyl)acetyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-(2-thienyl) acetic acid (40 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-(2-thienyl)ethanoyl isothiocyanate was prepared using the resultant 2-(2-thienyl)ethanoyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-(2-thienyl)ethanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (46 mg, yield 57%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.79 (s, 6H), 3.98 (d, J=6.34 Hz, 2H), 6.68 (d, J=9.03 Hz, 2H), 6.96-7.00 (m, 3H), 7.34-7.39 (m, 5H), 9.19 (s, 1H), 9.92 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 1173 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(4-methoxybenzoyl)thiourea

4-Methoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-methoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-methoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (36 mg, yield 46%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.92 (s, 9H), 7.09 (d, J=8.78 Hz, 1H), 7.19-7.22 (m, 3H), 7.31-7.36 (m, 2H), 7.43 (s, 1H), 7.48 (s, 1H), 8.06 (d, J=8.78 Hz, 1H), 8.12 (d, J=9.03 Hz, 1H), 8.53-8.57 (m, 1H), 11.52 (bs, 1H), 12.55 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 1174 N-(4-Chlorobenzoyl)-N′-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 4-chloro-1-benzenecarbonyl isothiocyanate was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (49 mg, yield 61%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.92 (s, 3H), 3.93 (s, 3H), 6.66 (d, J=5.12 Hz, 1H), 7.19-7.21 (m, 2H), 7.32-7.36 (m, 1H), 7.43 (s, 1H), 7.47 (s, 1H), 7.48 (s, 1H), 7.63 (d, J=8.78 Hz, 1H), 8.03 (d, J=8.78 Hz, 2H), 8.57 (d, J=5.12 Hz, 1H), 11.96 (bs, 1H), 12.57 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 529 (M⁺+1)

Example 1175 N-(2,4-Dimethoxybenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

2,4-Dimethoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-dimethoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,4-dimethoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (51 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.90 (s, 3H), 3.98 (s, 3H), 3.99 (s, 3H), 4.07 (s, 3H), 6.79-6.81 (m, 2H), 7.37-7.40 (m, 3H), 7.58 (s, 1H), 7.79-7.81 (m, 2H), 8.00 (d, J=9.03 Hz, 1H), 8.58 (s, 1H), 11.01 (bs, 1H), 12.68 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 521 (M⁺+1)

Example 1176 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2,4-dimethoxybenzoyl)thiourea

2,4-Dimethoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-dimethoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Chloro-4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,4-dimethoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (40 mg, yield 48%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.96 (s, 3H), 4.05 (s, 3H), 4.06 (s, 3H), 6.66 (d, J=5.12 Hz, 1H), 6.78-6.81 (m, 2H), 7.36 (s, 1H), 7.43 (s, 1H), 7.48 (s, 1H), 7.61 (s, 1H), 8.01 (d, J=8.54 Hz, 1H), 8.19 (d, J=9.03 Hz, 1H), 8.56 (d, J=5.12 Hz, 1H), 11.18 (bs, 1H), 12.67 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 555 (M⁺+1)

Example 1177 Ethyl 5-[({4-[(6,7-dimethoxy-4-quinazolinyl)oxy]anilino}carbothioyl)amino]-5-oxopentanoate

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 5-ethoxy-5-oxopentanoic acid (40 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and ethyl 5-isothiocyanat-5-oxopentanoate was prepared using the resultant ethyl 5-chloro-5-oxopentanoate as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of ethyl 5-isothiocyanat-5-oxopentanoate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (39 mg, yield 47%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.16-1.22 (m, 3H), 1.78-1.91 (m, 2H), 2.32-2.47 (m, 2H), 2.48-2.54 (m, 2H), 3.92 (s, 3H), 3.95 (s, 3H), 4.03-4.09 (m, 2H), 6.76 (d, J=8.78 Hz, 1H), 7.29-7.39 (m, 4H), 7.52 (s, 1H), 7.73 (d, J=5.37 Hz, 1H), 11.49 (s, 1H), 12.47 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 499 (M⁺+1)

Example 1178 Ethyl 4-[({4-[(6,7-dimethoxy-4-quinazolinyl)oxy]anilino}carbothioyl)amino]-4-oxobutanoate

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-ethoxy-5-oxobutanoic acid (40 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and ethyl 4-isothiocyanat-4-oxobutanoate was prepared using the resultant ethyl 4-chloro-4-oxobutanoate as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of ethyl 4-isothiocyanat-4-oxobutanoate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (38 mg, yield 47%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.16-1.24 (m, 3H), 2.51-2.63 (m, 2H), 2.73-2.78 (m, 2H), 3.92 (s, 3H), 3.95 (s, 3H), 4.02-4.11 (m, 2H), 7.29-7.39 (m, 3H), 7.57 (s, 1H), 7.70-7.74 (m, 2H), 8.62 (s, 1H), 11.60 (s, 1H), 12.38 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 485 (M⁺+1)

Example 1179 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-cyclohexylcarbonylthiourea

1-Cyclohexanecarbonyl isothiocyanate was prepared using commercially available 1-cyclohexanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 1-Cyclohexanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (44 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.16-1.41 (m, 6H), 1.66-1.85 (m, 4H), 2.55-2.61 (m, 1H), 3.94 (s, 3H), 3.95 (s, 3H), 6.41 (d, J=5.1 Hz, 1H), 7.42 (s, 1H), 7.46 (d, J=8.8 Hz, 1H), 7.52 (s, 1H), 7.68 (dd, J=2.2 Hz, 8.5 Hz, 1H), 8.15 (d, J=2.2 Hz, 1H), 8.50 (d, J=5.1 Hz, 1H), 11.51 (s, 1H), 12.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 500 (M⁺+1)

Example 1180 N-Cyclohexylcarbonyl-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

1-Cyclohexanecarbonyl isothiocyanate was prepared using commercially available 1-cyclohexanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 1-Cyclohexanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (48 mg, yield 62%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.16-1.45 (m, 6H), 1.66-1.86 (m, 4H), 2.55-2.61 (m, 1H), 3.98 (s, 3H), 3.99 (s, 3H), 7.34 (d, J=15.6 Hz, 2H), 7.39 (s, 1H), 7.56 (s, 1H), 7.73 (d, J=9.0 Hz, 2H), 8.56 (s, 1H), 11.41 (s, 1H), 12.55 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 467 (M⁺+1)

Example 1181 N-Cyclopropylcarbonyl-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

1-Cyclopropanecarbonyl isothiocyanate was prepared using commercially available 1-cyclopropanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 1-Cyclopropanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (51 mg, yield. 71%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.95-0.99 (m, 4H), 2.10-2.14 (m, 1H), 3.98 (s, 3H), 3.99 (s, 3H), 7.34 (d, J=9.0 Hz, 2H), 7.39 (s, 1H), 7.56 (s, 1H), 7.71 (d, J=8.8 Hz, 2H), 8.56 (s, 1H), 11.81 (s, 1H), 12.53 (s, 1H)

Mass spectrometry value (ESI-MS, m/z)

Example 1182 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-cyclopentylcarbonylthiourea

1-Cyclopentanecarbonyl isothiocyanate was prepared using commercially available 1-cyclopentanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 1-Cyclopentanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (38 mg, yield 52%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.56-1.76 (m, 6H), 1.88-1.90 (m, 2H), 2.97-3.03 (m, 1H), 3.94 (s, 3H), 3.96 (s, 3H), 6.40 (d, J=5.1 Hz, 1H), 7.42 (s, 1H), 7.46 (d, J=8.8 Hz, 1H), 7.52 (s, 1H), 7.68 (dd, J=2.7 Hz, 8.8 Hz, 1H), 8.15 (d, J=2.4 Hz, 1H), 8.50 (d, J=5.4 Hz, 1H), 11.56 (s, 1H), 12.60 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 486 (M⁺+1)

Example 1183 N-Cyclopentylcarbonyl-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

1-Cyclopentanecarbonyl isothiocyanate was prepared using commercially available 1-cyclopentanecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 1-Cyclopentanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (24 mg, yield 31%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.55-1.90 (m, 8H), 2.99-3.03 (m, 1H), 3.98 (s, 3H), 3.99 (s, 3H), 7.34 (d, J=8.8 Hz, 2H), 7.39 (s, 1H), 7.57 (s, 1H), 7.73 (d, J=8.8 Hz, 2H), 8.56 (s, 1H), 11.47 (s, 1H), 12.56 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 453 (M⁺+1)

Example 1184 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[3-(3-methylphenyl)propanoyl]-thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-(3-methylphenyl)propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-(3-methylphenyl)propanoyl isothiocyanate was prepared using the resultant 3-(3-methylphenyl)propanoyl chloride as a starting compound according to the description of the literature. 3-(3-Methylphenyl)propanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (31 mg, yield 38%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.29 (s, 3H), 2.77-2.89 (m, 4H), 3.94 (s, 3H), 3.96 (s, 3H), 6.41 (d, J=5.4 Hz, 1H), 7.01-7.08 (m, 3H), 7.19 (t, J=7.6 Hz, 1H), 7.42 (s, 1H), 7.47 (d, J=8.8 Hz, 1H), 7.53 (s, 1H), 7.67 (dd, J=2.4 Hz, 8.5 Hz, 1H), 8.13 (d, J=2.7 Hz, 1H), 8.50 (d, J=5.1 Hz, 1H), 11.62 (s, 1H), 12.53 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 537 (M⁺+1)

Example 1185 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[3-(3-methylphenyl)propanoyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 3-(3-methylphenyl)propanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 3-(3-methylphenyl)propanoyl isothiocyanate was prepared using the resultant 3-(3-methylphenyl)propanoyl chloride as a starting compound according to the description of the literature. 3-(3-Methylphenyl)propanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (32 mg, yield 38%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.29 (S, 3H), 2.77-2.87 (m, 4H), 3.98 (s, 3H), 3.99 (s, 3H), 7.01-7.08 (m, 3H), 7.19 (t, J=7.6 Hz, 1H), 7.34 (d, J=8.8 Hz, 2H), 7.39 (s, 1H), 7.57 (s, 1H), 7.72 (d, J=8.8 Hz, 2H), 8.56 (s, 1H), 11.52 (s, 1H), 12.50 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 503 (M⁺+1)

Example 1186 N-(4-Chlorobutanoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

4-Chlorobutanoyl isothiocyanate was prepared using commercially available 4-chlorobutanoyl chloride (80 mg) as a starting compound according to the description of the literature. 4-Chlorobutanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (30 mg, yield 38%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.04 (t, J=6.8 Hz, 2H), 2.65 (t, J=7.3 Hz, 2H), 3.70 (t, J=6.6 Hz, 2H), 3.98 (s, 3H), 3.99 (s, 3H), 7.35 (d, J=8.8 Hz, 2H), 7.39 (s, 1H), 7.57 (s, 1H), 7.72 (d, J=8.8 Hz, 2H), 8.56 (s, 1H), 11.55 (s, 1H), 12.45 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 461 (M⁺+1)

Example 1187 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2,2-dimethylpropanoyl)thiourea

2,2-Dimethylpropanoyl isothiocyanate was prepared using commercially available 2,2-dimethylpropanoyl chloride (80 mg) as a starting compound according to the description of the literature. 2,2-Dimethylpropanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (31 mg, yield 43%).

¹H-NMR (DMSO-d₆, 400 MHz): 1.27 (s, 9H), 3.94 (s, 3H), 3.96 (s, 3H), 6.41 (d, J=5.1 Hz, 1H), 7.42 (s, 1H), 7.47 (d, J=8.8 Hz, 1H), 7.52 (s, 1H), 7.68 (dd, J=2.4 Hz, 8.8 Hz, 1H), 8.12 (s, 1H), 8.51 (d, J=5.1 Hz, 1H), 10.78 (s, 1H), 12.50 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 474 (M⁺+1)

Example 1188 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2,2-dimethylpropanoyl)thiourea

2,2-Dimethylpropanoyl isothiocyanate was prepared using commercially available 2,2-dimethylpropanoyl chloride (80 mg) as a starting compound according to the description of the literature. 2,2-Dimethylpropanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (43 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.28 (s, 9H), 3.98 (s, 3H), 3.99 (s, 3H), 7.35 (d, J=8.8 Hz, 2H), 7.39 (s, 1H), 7.57 (s, 1H), 7.72 (d, J=8.5 Hz, 2H), 8.57 (s, 1H), 10.66 (s, 1H), 12.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z) 441 (M⁺+1)

Example 1189 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-hexanoylthiourea

Hexanoyl isothiocyanate was prepared using commercially available hexanoyl chloride (80 mg) as a starting compound according to the description of the literature. Hexanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (10 mg, yield 13%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.84-0.91 (m, 3H), 1.22-1.32 (m, 4H), 1.45-1.64 (m, 2H), 2.18 (t, J=7.3 Hz, 2H), 3.98 (s, 3H), 3.99 (s, 3H), 7.33-7.37 (m, 2H), 7.39 (s, 1H), 7.57 (s, 1H), 7.70-7.75 (m, 2H), 8.56 (s, 1H), 11.45 (s, 1H), 12.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 455 (M⁺+1)

Example 1190 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[(2-methylcyclopropyl)carbonyl]-thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-methyl-1-cyclopropanecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-methyl-1-cyclopropanecarbonyl isothiocyanate was prepared using the resultant 2-methyl-1-cyclopropanecarbonyl chloride as a starting compound according to the description of the literature. 2-Methyl-1-cyclopropanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]-aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (40 mg, yield 56%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.84-0.89 (m, 1H), 1.08-1.38 (m, 5H), 1.87-1.91 (m, 1H), 3.94 (s, 3H), 3.95 (s, 3H), 6.40 (d, J=5.1 Hz, 1H), 7.42 (s, 1H), 7.46 (d, J=8.8 Hz, 1H), 7.52 (s, 1H), 7.66 (dd, J=2.7 Hz, 8.8 Hz, 1H), 8.13 (d, J=2.4 Hz, 1H), 8.49 (d, J=5.4 Hz, 1H), 11.82 (s, 1H), 12.58 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 472 (M⁺+1)

Example 1191 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[(2-methylcyclopropyl)carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-methyl-1-cyclopropanecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-methyl-1-cyclopropanecarbonyl isothiocyanate was prepared using the resultant 2-methyl-1-cyclopropanecarbonyl chloride as a starting compound according to the description of the literature. 2-Methyl-1-cyclopropanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (13 mg, yield 18%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.84-0.88 (m, 1H), 1.09-1.24 (m, 5H), 1.88-1.90 (m, 1H), 3.98 (s, 3H), 3.99 (s, 3H), 7.33 (d, J=9.0 Hz, 2H), 7.39 (s, 1H), 7.56 (s, 1H), 7.71 (d, J=9.0 Hz, 2H), 8.56 (s, 1H), 11.73 (s, 1H), 12.54 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 439 (M⁺+1)

Example 1192 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[(1-methylcyclohexyl)carbonyl]-thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 1-methyl-1-cyclohexanecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 1-methyl-1-cyclohexanecarbonyl isothiocyanate was prepared using the resultant 1-methyl-1-cyclohexanecarbonyl chloride as a starting compound according to the description of the literature. 1-Methyl-1-cyclohexanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (38 mg, yield 49%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.26 (s, 3H), 1.35-1.52 (m, 8H), 2.06-2.09 (m, 2H), 3.94 (s, 3H), 3.96 (s, 3H), 6.41 (d, J=5.1 Hz, 1H), 7.42 (s, 1H), 7.47 (d, J=8.8 Hz, 1H), 7.52 (s, 1H), 7.68-7.72 (m, 1H), 8.15 (s, 1H), 8.50 (d, J=5.1 Hz, 1H), 10.66 (s, 1H), 12.65 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 515 (M⁺+1)

Example 1193 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[(1-methylcyclohexyl)carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 1-methyl-1-cyclohexanecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 1-methyl-1-cyclohexanecarbonyl isothiocyanate was prepared using the resultant 1-methyl-1-cyclohexanecarbonyl chloride as a starting compound according to the description of the literature. 1-Methyl-1-cyclohexanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (31 mg, yield 38%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.26 (s, 3H), 1.38-1.52 (m, 8H), 2.05-2.11 (m, 2H), 3.98 (s, 3H), 3.99 (s, 3H), 7.35 (d, J=8.8 Hz, 2H), 7.39 (s, 1H), 7.57 (s, 1H), 7.74 (d, J=8.8 Hz, 2H), 8.57 (s, 1H), 10.54 (s, 1H), 12.62 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 481 (M⁺+1)

Example 1194 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[(1-phenylcyclopropyl)carbonyl]-thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 1-phenyl-1-cyclopropanecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 1-phenyl-1-cyclopropanecarbonyl isothiocyanate was prepared using the resultant 1-phenyl-1-cyclopropanecarbonyl chloride as a starting compound according to the description of the literature. 1-Phenyl-1-cyclopropanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (24 mg, yield 30%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.34 (s, 2H), 1.63 (s, 2H), 3.94 (s, 3H), 3.95 (s, 3H), 6.40 (d, J=5.1 Hz, 1H), 7.42-7.55 (m, 7H), 7.66 (d, J=8.5 Hz, 1H), 8.07 (s, 1H), 8.50 (d, J=5.1 Hz, 1H), 9.22 (s, 1H), 12.28 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 534 (M⁺+1)

Example 1195 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[(1-phenylcyclopropyl)carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 1-phenyl-1-cyclopropanecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 1-phenyl-1-cyclopropanecarbonyl isothiocyanate was prepared using the resultant 1-phenyl-1-cyclopropanecarbonyl chloride as a starting compound according to the description of the literature. 1-Phenyl-1-cyclopropanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (58 mg, yield 69%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.34 (s, 2H), 1.64 (s, 2H), 3.97 (s, 3H), 3.99 (s, 3H), 7.32-7.55 (m, 8H), 7.69 (d, J=7.3 Hz, 2H), 8.55 (s, 1H), 9.00 (s, 1H), 12.25 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 501 (M⁺+1)

Example 1196 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-[(4-propylcyclohexyl)carbonyl]-thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-propyl-1-cyclohexanecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-propyl-1-cyclohexanecarbonyl isothiocyanate was prepared using the resultant 4-propyl-1-cyclohexanecarbonyl chloride as a starting compound according to the description of the literature. 4-Propyl-1-cyclohexanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (51 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.85-0.94 (m, 5H), 1.07-1.44 (m, 7H), 1.77-1.89 (m, 4H), 2.66-2.70 (m, 1H), 3.95 (s, 3H), 3.96 (s, 3H), 6.41 (d, J=5.1 Hz, 1H), 7.43 (s, 1H), 7.47 (d, J=8.8 Hz, 1H), 7.53 (s, 1H), 7.67-7.73 (m, 1H), 8.14-8.19 (m, 1H), 8.49-8.53 (m, 1H), 11.53 (s, 1H), 12.58 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 542 (M⁺+1)

Example 1197 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-[(4-propylcyclohexyl)carbonyl]thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-propyl-1-cyclohexanecarboxylic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-propyl-1-cyclohexanecarbonyl isothiocyanate was prepared using the resultant 4-propyl-1-cyclohexanecarbonyl chloride as a starting compound according to the description of the literature. 4-Propyl-1-cyclohexanecarbonyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by thin-layer chromatography using chloroform/acetone for development to give the title compound (59 mg, yield 69%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.85-0.91 (m, 5H), 1.15-1.41 (m, 7H), 1.78-1.89 (m, 4H), 2.66-2.69 (m, 1H), 3.98 (s, 3H), 3.99 (s, 3H), 7.35 (d, J=6.6 Hz, 2H), 7.40 (s, 1H), 7.57 (s, 1H), 7.71-7.77 (m, 2H), 8.57 (s, 1H), 11.43 (s, 1H), 12.55 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 509 (M⁺+1)

Example 1198 N-(4-Chlorobutanoyl)-N′-{3-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}thiourea

4-Chlorobutanoyl isothiocyanate was prepared using commercially available 4-chlorobutanoyl chloride (80 mg) as a starting compound according to the description of the literature. 4-Chlorobutanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (35 mg, yield 48%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.00-2.08 (m, 2H), 2.66 (t, J=7.1 Hz, 2H), 3.71 (t, J=6.6 Hz, 2H), 3.99 (s, 3H), 4.00 (s, 3H), 6.60-6.65 (m, 1H), 7.51 (s, 1H), 7.56 (d, J=8.8 Hz, 1H), 7.64 (s, 1H), 7.73-7.78 (m, 1H), 8.18-8.23 (m, 1H), 8.67 (d, J=5.6 Hz, 1H), 11.67 (s, 1H), 12.50 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 495 (M⁺+1)

Example 1199 N-(3-Chloropropanoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

3-Chloropropanoyl isothiocyanate was prepared using commercially available 3-chloropropanoyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloropropanoyl isothiocyanate thus obtained was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (38 mg, yield 50%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.04 (t, J=4.6 Hz, 2H), 3.88 (t, J=3.7 Hz, 2H), 3.99 (s, 3H), 4.00 (s, 3H), 7.37 (d, J=6.6 Hz, 2H), 7.40 (s, 1H), 7.58 (s, 1H), 7.73 (d, J=6.3 Hz, 2H), 8.57 (s, 1H), 11.65 (s, 1H), 12.39 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 447 (M⁺+1)

Example 1200 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-methylpentanoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 2-methylpentanoic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 2-methylpentanoyl isothiocyanate was prepared using the resultant 2-methylpentanoyl chloride as a starting compound according to the description of the literature. The resultant 2-methylpentanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (69 mg, yield 94%).

¹H-NMR (chloroform-d, 400 MHz): δ 0.85-1.80 (m, 10H), 2.37-2.53 (m, 1H), 4.09 (s, 3H), 4.11 (s, 3H), 6.49 (d, J=5.9 Hz, 1H), 7.31 (d, J=5.1 Hz, 1H), 7.61 (s, 1H), 7.72 (dd, J=2.4 Hz, 8.8 Hz, 1H), 7.76 (s, 1H), 8.08 (d, J=2.4 Hz, 1H), 8.66 (s, 1H), 12.66 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 488 (M⁺+1)

Example 1201 N-{4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]phenyl}-N′-(2-methylpentanoyl)thiourea

2-Methylpentanoyl isothiocyanate prepared according to the method 2 was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 16 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (44 mg, yield 57%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.87-0.92 (m, 3H), 1.09-1.13 (m, 3H), 1.26-1.65 (m, 4H), 2.74-2.81 (m, 1H), 3.98 (s, 3H), 4.00 (s, 3H), 7.34-7.38 (m, 2H), 7.40 (s, 1H), 7.57 (s, 1H), 7.72-7.78 (m, 2H), 8.57 (s, 1H), 11.51 (s, 1H), 12.59 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 455 (M⁺+1)

Example 1202 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2,4-difluorobenzoyl)thiourea

2,4-Difluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-difluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,4-difluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (42 mg, yield 53%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.93 (s, 3H), 3.96 (s, 3H), 6.66 (d, J=5.12 Hz, 1H), 7.16-7.36 (m, 5H), 7.61 (s, 1H), 7.82-7.83 (m, 1H), 8.10 (d, J=9.03 Hz, 1H), 8.56 (d, J=5.12 Hz, 1H), 11.98 (bs, 1H), 12.33 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 530 (M⁺+1)

Example 1203 N-(3,4-Dimethoxybenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

3,4-Dimethoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3,4-dimethoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3,4-dimethoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (57 mg, yield 65%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.79 (s, 3H), 3.83 (s, 3H), 3.96 (s, 3H), 3.99 (s, 3H), 6.62 (d, J=15.61 Hz, 2H), 6.92 (d, J=15.61 Hz, 2H), 7.04 (d, J=8.54 Hz, 1H), 7.38 (s, 1H), 7.44 (s, 1H), 7.52 (s, 1H), 7.56 (dd, J=2.19 Hz, J=8.30 Hz, 1H), 8.56 (s, 1H), 11.88 (bs, 1H), 12.50 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 521 (M⁺+1)

Example 1204 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(3,4-dimethoxybenzoyl)thiourea

3,4-Dimethoxy-1-benzenecarbonyl isothiocyanate was prepared using commercially available 3,4-dimethoxy-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 3,4-dimethoxy-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (49 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.79 (s, 3H), 3.83 (s, 3H), 3.93 (s, 3H), 3.94 (s, 3H), 5.46 (bs, 1H), 6.29 (d, J=15.37 Hz, 1H), 6.62-6.43 (m, 1H), 6.79 (s, 1H), 7.03-7.10 (m, 2H), 7.38 (s, 1H), 7.52 (s, 1H), 7.55-7.58 (m, 2H), 8.44 (d, J=5.12 Hz, 1H), 12.63 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 555 (M⁺+1)

Example 1205 N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2-phenylacetyl)thiourea

2-Phenylethanoyl isothiocyanate was prepared using commercially available 2-phenylethanoyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-phenylethanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (48 mg, yield 62%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.85 (s, 3H), 3.93 (s, 3H), 3.95 (s, 3H), 6.64 (d, J=5.08 Hz, 1H), 7.27-7.39 (m, 5H), 7.42 (s, 1H), 7.49 (s, 1H), 7.57 (s, 1H), 8.10 (d, J=8.78 Hz, 1H), 8.55 (d, J=5.38 Hz, 1H), 11.91 (bs, 1H), 12.39 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 508 (M⁺+1)

Example 1206 N-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-N′-(2-phenylacetyl)thiourea

2-Phenylethanoyl isothiocyanate was prepared using commercially available 2-phenylethanoyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-phenylethanoyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (44 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.08 (s, 3H), 2.15 (s, 3H), 3.85 (s, 2H), 3.94 (s, 3H), 3.95 (s, 3H), 6.28 (d, J=5.12 Hz, 1H), 7.08 (d, J=8.54 Hz, 1H), 7.27-7.41 (m, 7H), 7.57 (s, 1H), 8.47 (d, J=5.37 Hz, 1H), 11.75 (bs, 1H), 12.01 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 502 (M⁺+1)

Example 1207 N-(2,4-Dichlorobenzoyl)-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}thiourea

2,4-Dichloro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-dichloro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,4-dichloro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (65 mg, yield 73%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.97 (s, 3H), 3.99 (s, 3H), 7.38 (d, J=11.22 Hz, 3H), 7.55-7.58 (m, 2H), 7.69 (d, J=8.29 Hz, 1H), 7.76-7.78 (m, 3H), 8.57 (s, 1H), 12.04 (bs, 1H), 12.26 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 530 (M⁺+1)

Example 1208 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2,4-difluorobenzoyl)thiourea

2,4-Difluoro-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2,4-difluoro-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2,4-difluoro-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (50 mg, yield 63%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 3.95 (s, 3H), 3.96 (s, 3H), 6.43 (d, J=5.37 Hz, 1H), 7.24-7.29 (m, 1H), 7.43-7.55 (m, 3H), 7.75 (dd, J=2.44 Hz, J=8.78 Hz, 1H), 7.79-7.90 (m, 2H), 8.16 (bs, 1H), 8.52 (d, J=5.12 Hz, 1H), 11.86 (bs, 1H), 12.32 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 530 (M⁺+1)

Example 1209 N-{3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(4-octylbenzoyl)thiourea

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 4-octylbenzoic acid (40 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 4-octyl-1-benzenecarbonyl isothiocyanate was prepared using the resultant 4-octyl-1-benzenecarbonyl chloride as a starting compound according to the description of the literature. 3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]-aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-octyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (53 mg, yield 58%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.84-0.87 (m, 4H), 1.60 (m, 2H), 2.09 (s, 2H), 2.50 (s, 7H), 2.65-2.69 (m, 2H), 3.94 (s, 3H), 5.46 (bs, 1H), 6.29 (d, J=15.37 Hz, 1H), 6.42 (d, J=5.12 Hz, 1H), 7.36-7.54 (m, 6H), 7.74-7.76 (m, 1H), 7.94 (d, J=8.05 Hz, 2H), 8.19 (bs, 1H), 8.51 (d, J=5.12 Hz, 1H), 11.61 (bs, 1H), 12.70 (bs, 1H)

Mass spectrometry value (ESI-MS, m/z): 607 (M⁺+1)

Example 1210 N-4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-nitrophenyl-N′-(4-piperidinobutyl)urea

Piperidine (357 mg) was dissolved in acetonitrile (20 ml) to prepare a solution. Potassium carbonate (97 mg) was then added to the solution. 2-(4-Bromobutyl)-1,3-isoindolinedione (1 g) was further added thereto, and the mixture was stirred with heating under reflux for 10 hr. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and brine. The extract was then dried over sodium sulfate, was filtered, and was concentrated to give 850 mg of a mixture containing 2-(4-piperidinobutyl)-1,3-isoindolinedione. The mixture containing 2-(4-piperidinobutyl)-1,3-isoindolinedione (850 mg) thus obtained was dissolved in ethyl alcohol (10 ml) to prepare a solution. Hydrazine monohydrate (0.75 ml) was then added to the solution, and the mixture was stirred at room temperature for one hr. This solution was concentrated to give 980 mg of a mixture containing 4-piperidinobutylamine. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) to prepare a solution. Triethylamine (1 ml) was then added to the solution, and a solution of triphosgene (131 mg) in chloroform (5 ml) was further added thereto. The mixture was stirred at room temperature for 10 min. A solution of the mixture containing 4-piperidinobutylamine (69 mg) in chloroform (5 ml) was then added thereto, and the mixture was stirred at room temperature for 30 min. Water was added to stop the reaction, the reaction solution was then extracted with chloroform, and the extract was dried over sodium sulfate. The extract was filtered and concentrated. The powder thus obtained was then filtered and washed with diethyl ether to give N-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl-N′-(4-piperidinobutyl)-urea (104 mg, yield 68%).

¹H-NMR (CDCl₃, 400 MHz): δ 1.54 (brs, 2H), 1.65-1.79 (m, 8H), 2.52-2.61 (m, 6H), 3.35 (t, J=5.9 Hz, 2H), 4.075 (s, 3H), 4.080 (s, 3H), 7.00 (brs, 1H), 7.34 (s, 1H), 7.51-7.54 (m, 2H), 8.12 (d, J=2.7 Hz, 1H), 8.61 (s, 1H), 8.76 (d, J=9.5 Hz, 1H), 9.73 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 525 (M⁺+1)

Example 1211 N-4-[(6,7-Dimethoxy-4-quinazolinyl)-oxy]-2-nitrophenyl-N′-(4-piperidinopropyl)urea

Piperidine (357 mg) was dissolved in acetonitrile (20 ml) to prepare a solution. Potassium carbonate (97 mg) was then added to the solution. Further, 2-(3-bromopropyl)-1,3-isoindolinedione (1 g) was added thereto, and the mixture was stirred with heating under reflux for 10 hr. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and brine. The extract was then dried over sodium sulfate, was filtered, and was concentrated to give 850 mg of a mixture containing 2-(3-piperidinopropyl)-1,3-isoindolinedione. The mixture containing 2-(3-piperidinopropyl)-1,3-isoindolinedione (850 mg) thus obtained was dissolved in ethyl alcohol (10 ml) to prepare a solution. Hydrazine monohydrate (0.75 ml) was then added to the solution, and the mixture was stirred at room temperature for one hr. This solution was concentrated to give 980 mg of a mixture containing 3-piperidinobutylamine. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]-2-nitroaniline (100 mg) was dissolved in chloroform (10 ml) to prepare a solution. Triethylamine (1 ml) was then added to the solution. A solution of triphosgene (131 mg) in chloroform (5 ml) was further added to the solution, and the mixture was stirred at room temperature for 10 min. A solution of the mixture containing 3-piperidinopropylamine (69 mg) in chloroform (5 ml) was then added thereto, and the mixture was stirred at room temperature for 30 min. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with sodium sulfate. The extract was then filtered and was concentrated to give a powder. The powder was then filtered and was washed with diethyl ether to give N-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl-N′-(3-piperidinopropyl)-urea (104 mg, yield 68%).

¹H-NMR (CDCl₃, 400 MHz): δ 1.55 (brs, 2H), 1.65-1.80 (m, 6H), 2.50-2.62 (m, 6H), 3.37 (t, J=5.9 Hz, 2H), 4.075 (s, 3H), 4.080 (s, 3H), 7.05 (brs, 1H), 7.35 (s, 1H), 7.50-7.55 (m, 2H), 8.10 (d, J=2.7 Hz, 1H), 8.60 (s, 1H), 8.78 (d, J=9.5 Hz, 1H), 9.75 (s, 1H)

Mass spectrometry value (ESI-MS, m/z): 511 (M⁺+1)

Pharmacological Test Example 1 Measurement of Inhibitory Activity Against PDGF-Ra Phosphorylation by PDGF-AA Stimulation Using G292

G-292 human osteosarcoma cells (Dainippon Pharmaceutical Co. Ltd.) were cultured in a DMEM medium (Dainippon Pharmaceutical Co. Ltd.) containing 10% FBS within an incubator containing 5% carbon dioxide until 80% confluent, and the cells were planted at 3×10⁴ cells per well in 96-well flat-bottom plates in the same medium containing 0.1% FBS. After cultivation at 37° C. overnight, a solution of a test compound in dimethyl sulfoxide was added to each well, and a reaction was allowed to proceed at 37° C. for one hr.

After the reaction of the test compound, PDGF-AA (Upstate) was added to 50 ng/ml, and the cells were stimulated at 37° C. for 5 min. Thereafter, the cells were solubilized and shaken at room temperature for 20 min.

This solubilized cell solution was transferred to a 96-well plate coated with aniti-phosphotyrosine antibody PY-20, and a reaction was allowed to proceed at 4° C. overnight. Anti-PDGF-Ra (c-20) (Santa Cruz) was added as a primary antibody, and a reaction was allowed to proceed for one hr. GAR (Anti-rabbit Ig, horseradish peroxidase, Amersham) was then added as a secondary antibody, and a reaction was allowed to proceed for one hr. Color development was carried out using a color development kit for peroxidase (Sumitomo Bakelite Co., Ltd.), and the absorbance was measured at 450 nm. The phosphorylation of PDGF-Ra in the presence of the test compound was measured by presuming a phosphorylation degree of the receptor in the presence of a ligand to be 100% and a phosphorylation degree of PDGF-Ra in the absence of a ligand to be 0%, and IC₅₀ was then determined.

Pharmacological Test Example 2 PDGF-R Autophosphorylation Inhibition Screening (Dot Plotting)

Vascular smooth muscle cells (passage 5 to 10) collected from rat thoracic aorta by the explant method were planted at 8×10³ cells per well in 96-well plates, subject to a serum starvation state, and 24 hr after the plantation then assayed.

A test compund was added, and the mixture was incubated at 37° C. for one hr. Thereafter, PDGF-BB was added to 50 ng/ml, and the mixture was incubated for 5 min, followed by washing with cold PBS. Lysate buffer (20 μl/well) was then added, SDS buffer (20 ml/well) was added thereto, and 2 μl of the mixture was then spotted on a PDVF membrane.

Treatment was carried out with anti-mouse IgG which had been labelled with peroxidase after treatment with an anti-phosphotyrosine antibody, followed by development in an ECL color development kit (Amersham). Thereafter, the color intensity was quantitatively determined by image analysis.

The inhibitory activity IC₅₀ of the test compound was calculated by presuming a color intensity with the addition of PDGF and without the addition of the test compound to be 0% inhibition and a color intensity without the test compound and PDGF to be 100% inhibition.

Pharmacological Test Example 3 Inhibitory Activity Against c-Kit Autophosphorylation

MO7e (human megakaryocytic leukemia cell line) which had been arrested for 20 hr was seeded into 96 well plates at an amount of 2×10⁵ per well. A solution of a test compound in DMSO was added, and a reaction was then allowed to proceed for one hr. Thereafter, the cells were stimulated by 50 ng/ml of h-SCF for 5 min, followed by replacement with lysate buffer to solubilize the cells.

Next, the solubilized cell sap was transferred to a 96-well plate with an anti-phosphotyrosine antibody (PY-20) previously immobilized thereon, and a reaction was allowed to proceed. Thereafter, the cells were reacted with an anti-c-kit antibody (c-19, Santa Cruz) as a primary antibody and were labelled with GAR (anti-rabbit IgG, horseradish peroxidase, Amersham) as a secondary antibody. Color development was then carried out in a peroxidase color development kit (Sumitomo Bakelite Co., Ltd.), and the absorbance was measured at a wavelength of 450 nm.

The c-kit autophosphorylation inhibitory activity of the test compound was measured by presuming c-kit autophosphorylation activity with the addition of DMSO in the absence of h-SCF to be 100% inhibition and c-kit autophosphorylation activity with the addition of DMSO in the presence of h-SCF to be 0% inhibition, and IC₅₀ was then determined.

The results of Pharmacological Test Examples 1 to 3 were as follows. Values within parentheses indicates IC₅₀ (nM). Figures within parenthesess in >100 ( ) in PDGF(E) indicate inhibition (%) at 100 nM. Figures within parentheses in >1000 ( ) and −( ) indicate inhibition (%) at 1000 nM. Figures within parentheses in −( ) of c-kit indicate inhibition (%) at 1000 nM. The symbol > indicates that the inhibition at an indicated concentration is not more than 50%. The symbols < and << indicate that the inhibition at an indicated concentration is not less than 50%. Example No. PDGF (E) PDGF (D) c-kit 1 <10 52 2 17 422 3 <10 173 4 <10 133 5 24 336 6 <10 175 7 12 616 8 <<10 62 9 <10 45 10 11 106 11 <<10 36 12 11 389 13 <10 135 14 12 209 15 21 −(48) 16 <10 495 17 <10 57 18 22 93 19 <<10 41 20 <<10 109 21 <10 135 22 <10 186 23 <10 475 24 <<10 129 25 <10 566 26 <<10 44 27 <<10 76 28 <10 118 29 27 121 30 <10 <30 31 <10 221 32 16 227 33 23 362 34 >100 (45) 800 35 <10 342 36 >100 (34) −(19) 37 <<10 <30 38 <10 33 39 <10 56 40 <<10 55 41 <10 185 42 <10 73 43 <10 158 44 19 328 45 <10 91 46 22 388 47 <10 178 48 <10 162 49 <10 185 50 <10 50 51 14 270 52 <10 273 53 <10 480 54 15 473 55 <10 288 56 11 774 57 11 393 58 12 499 59 57 −(33) 60 <10 261 61 10 −(32) 62 13 70 63 16 211 64 90 429 65 <10 103 66 50 353 67 <10 342 68 13 294 69 53 755 70 <10 451 71 38 −(34) 72 36 387 73 28 235 74 100 1000 75 25 1000 76 >100 (37) −(14) 77 <10 99 78 16 129 79 18 123 80 12 137 81 12 408 82 10 176 83 16 253 84 27 399 85 <10 163 86 13 842 87 <10 607 88 19 −(45) 89 14 −(35) 90 <10 621 91 14 −(20) 92 <10 677 93 17 601 94 31 −(31) 95 16 962 96 38 −(13) 97 <10 254 98 <10 152 99 21 394 100 14 815 101 12 −(27) 102 <10 217 103 15 200 104 25 590 105 <10 252 106 12 1000 107 372 108 180 109 412 110 110 111 750 112 16 214 113 18 402 114 65 602 115 <10 387 116 31 1000 117 26 759 118 33 746 119 >100 −(31) 120 13 505 121 48 −(17) 122 11 821 123 <10 207 124 42 −(39) 125 <10 671 126 19 −(10) 127 16 283 128 26 375 129 64 732 130 <10 714 131 38 −(40) 132 26 301 133 26 206 134 >100 (49) 944 135 18 475 136 43  −(7) 137 <10 233 138 17 74 139 57 80 140 <10 234 141 36 −(26) 142 <10 <30 143 <10 <30 144 18 49 145 <10 <30 146 11 32 147 11 <30 148 <10 <30 149 19 49 150 <10 38 151 12 32 152 <10 <30 153 <10 <30 154 40 61 155 14 41 156 >100 (48) 33 157 <10 35 158 12 107 159 52 147 160 16 52 161 <10 178 162 16 162 163 <10 185 164 12 50 165 49 149 166 34 145 167 45 370 168 15 52 169 <10 31 170 <10 34 171 22 83 172 17 74 173 <<10 37 174 <10 70 175 <<10 45 176 20 <30 177 19 <30 178 >100 179 70 180 63 181 >100 182 >100 183 35 706 184 38 369 185 46 186 63 187 <10 561 188 100 189 57 190 >100 191 84 503 192 56 193 57 194 91 715 195 66 196 49 197 93 198 21 1000 199 35 807 200 31 329 201 >100 202 10 610 203 25 169 204 28 79 205 78 206 13 80 207 31 55 208 18 53 209 >100 210 16 95 211 17 43 212 28 70 213 21 61 214 >30 (6) 47 215 8 <30 216 <3 19 217 29 39 218 88 123 219 27 <30 220 47 77 221 84 109 222 45 101 223 7 101 224 >100 147 225 86 453 226 11 72 227 7 194 228 10 71 229 18 47 230 8 111 231 1 86 232 11 42 233 8 52 234 10 46 235 <3 57 236 4 47 237 6 42 238 10 36 239 9 183 240 17 248 241 12 232 242 21 192 243 20 190 244 27 69 245 16 408 246 58 243 247 3 40 248 11 147 249 4 57 250 4 184 251 6 185 252 6 111 253 17 514 254 >100 (27) 396 255 >100 (36) 309 256 <3 15 257 6 22 258 3 178 259 34 184 260 6 180 261 4 44 262 7 83 263 10 329 264 42 486 265 35 122 266 6 34 267 23 35 268 6 34 269 17 −(48) 270 65 471 271 22 130 272 61 297 273 23 107 274 25 399 275 16 103 276 16 413 277 10 53 278 53 289 279 <10 <30 280 <10 370 281 >100 (49) 268 282 34 48 283 <10 121 284 <10 269 285 <10 85 286 <10 54 287 13 228 288 <10 162 289 <10 328 290 47 281 291 26 124 292 14 262 293 <10 145 294 15 109 295 >100 (45) 178 296 61 109 297 <<10 41 298 <10 119 299 <<10 53 300 <10 −(43) 301 43 −(39) 302 12 202 303 11 188 304 63 401 305 11 221 306 11 72 307 >100 (49) 165 308 20 101 309 10 285 310 67 607 311 <10 329 312 <<10 29 313 <10 330 314 44 32 315 <10 82 316 10 −(40) 317 <<10 136 318 10 418 319 <<10 98 320 <10 596 321 <<10 37 322 <10 60 323 <<10 <30 324 12 64 325 <10 46 326 >100 (31) −(18) 327 >100 (30)  −(6) 328 >100 (22) −(10) 329 <10 253 330 12 467 331 <10 377 332 <<10 259 333 12 712 334 <10 484 335 <<10 <30 336 14 109 337 <10 198 338 25 956 339 38 197 340 <10 107 341 32 519 342 <<10 <30 343 <10 232 344 <10 <30 345 30 123 346 41 −(37) 347 77 228 348 <10 90 349 12 309 350 <10 238 351 <10 64 352 <10 195 353 <10 80 354 15 384 355 24 252 356 <10 66 357 <10 116 358 <10 366 359 28 274 360 16 189 361 <10 278 362 42 −(26) 363 <10 72 364 29 98 365 <10 47 366 27 66 367 55 207 368 64 426 369 >100 −(36) 370 74 585 371 <10 541 372 −(14) 373 43 71 374 <10 <30 375 74 144 376 <10 41 377 21 151 378 14 92 379 11 624 380 <10 45 381 66 382 <10 28 383 74 90 384 >100 (37) 385 <10 87 386 20 105 387 <10 31 388 12 60 389 51 390 33 400 391 13 129 392 >100 (38) 432 393 82 90 394 <10 133 395 19 226 396 19 86 397 <10 77 398 33 462 399 63 327 400 <10 671 401 <10 586 403 14 93 404 <10 81 405 46 126 406 <10 <30 407 26 68 408 <10 192 409 26 392 410 12 79 411 17 43 412 81 122 413 39 50 414 >100 (27) 415 24 98 416 >100 (49) 417 >100 (42) 418 26 401 419 >100 (47) 420 16 77 421 <10 34 422 <10 119 423 <10 102 424 47 224 425 >100 (5)  464 426 22 272 427 >100 (13) 364 428 64 158 429 54 603 430 76 182 431 17 43 432 13 <30 433 11 <30 434 20 <30 435 33 445 436 >100 (46) 878 437 48 250 438 >100 (41) 414 439 52 224 440 47 351 441 70 1000 442 >100 (32) −(28) 443 15 627 444 21 972 445 >100 (11) 941 446 >100 (39) −(40) 447 >100 (11) 553 448 >100 (39) −(25) 449 >100 (26) 747 450 >100 (13) −(46) 451 >100 (25) 613 452 >100 (31) −(37) 453 >100 (1)  454 >100 (23) 455 77 456 >100 (21) 457 >100 (29) 458 >100 (18) 459 47 <30 460 >100 (15) 461 60 462 52 575 463 91 432 464 55 201 465 56 1000 466 >100 (16) 467 >100 (8)  468 >100 (20) 469 >100 (0)  −(28) 470 26 128 471 >100 (28) 237 472 31 67 473 >100 (30) 259 474 46  −(6) 475 15 −(24) 476 <10 172 477 59 248 478 17 −(28) 479 13 −(17) 480 10 −(22) 481 16  −(3) 482 24  −(5) 483 20 <30 484 12 75 485 >100 (35) 486 >100 (36) 487 >100 (31) 488 98 489 58 637 490 21 261 491 24 315 492 20 321 493 39 1000 494 16 125 495 65 496 45 −(32) 497 <10 82 498 <10 140 499 <10 98 500 14 199 501 11 56 502 −(23) 503 87 −(36) 504 46 −(42) 505 53 −(25) 506 74 369 507 44 787 508 −(28) 509 26 164 510 >100 (3)  −(17) 511 19 663 512 29 1000 513 >100 (28) 720 514 >100 (31) −(29) 515 >100 (32) −(21) 516 50 −(27) 517 38 −(33) 518 >100 (17) 519 >100 (22) 520 >100 (43) 521 >100 522 >100 523 >100 524 >100 (21) −(21) 525 79 −(41) 526 >100 (46) 731 527 65 875 528 33 343 529 >100 (38)  −(8) 530 >100 (45) −(34) 531 −(31) 532 >100 (44) 752 533 64 623 534 51 −(35) 535 32 −(27) 536  −(7) 537 >100 (34) −(34) 538 >100 (22) 768 539 >100 (45) 415 540 48 447 541 70 794 542 >100 (45) 442 543 54 328 544 <10 216 545 70 254 546 54 −(44) 547 >100 (33) −(41) 548 46 268 549 62 681 550 77 536 551 >100 (19) 1000 552 >100 (10) −(28) 553 >100 (40) 320 554 >100 (14) 555 >100 (29) −(39) 556 >100 (13) −(28) 557 >100 (33) 634 558 73 724 559 36 711 560 12 107 561 <10 54 562 80 −(27) 563 54 406 564 39 291 565 46 170 566 17 276 567 21 118 568 >100 (28) −(31) 569 12 168 570 23 173 571 32 556 572 64 262 573 39 348 574 45 147 575 27 664 576 36 151 577 14 328 578 18 104 579 22 145 580 14 84 581 14 180 582 >100 (20) −(29) 583 >100 (17) −(18) 584 >100 (13) −(13) 585 >100 (32) 1000 586 63 734 587 67 −(16) 588 36 1000 589 28 487 590 54 296 591 33 117 592 23 472 593 51 1000 594 >100 (39) −(10) 595 46 −(0) 596 63 719 597 >100 (27)  −(8) 598 19 423 600 <10 208 602 11 180 603 >100 (42) 864 604 73 322 605 31 394 606 18 263 607 29 554 608 <10 201 609 45 610 380 611 95 1073 612 10 173 613 56 −(29) 614 <10 434 615 17 125 616 36 224 617 <10 172 618 <10 948 619 >100 (49) −(44) 620 <10 519 621 30 −(30) 622 11 355 623 90 632 624 34 436 625 >100 (31) 596 626 49 339 627 65 774 628 <10 81 629 <10 481 630 36 −(23) 631 39 186 632 36 223 633 58 −(28) 634 >100 (40) −(13) 635 >100 (25) −(23) 636 33 106 637 52 375 638 >100 (43) −(16) 639 >100 (29) −(12) 640 35 254 641 28 293 642 >100 (20)  −(8) 643 >100 (40)  −(2) 644 >100 (17) −(14) 645 23 −(32) 646 11  −(0) 647 13 712 648 16 937 649 39 1000 650 32 420 651 40 808 652 43 115 653 23 581 654 19 698 655 43 −(43) 656 19 −(32) 657 40 −(27) 658 19 389 659 19 1000 660 25 835 661 <10 75 662 23 296 663 <10 202 664 <10 97 665 11 122 666 10 134 667 <10 100 668 <10 144 669 23 134 670 15 82 671 64 −(22) 672 53  −(9) 673 15 426 674 >100 (43) 854 675 46 442 676 26 632 677 47 730 678 <10 164 679 <10 337 680 35 570 681 30 270 682 >100 (30) −(32) 683 >100 (40) −(26) 684 52 549 685 22 −(41) 686 38 −(19) 687 26 −(34) 688 34 −(19) 689 >100 (42) 571 690 >100 (10) −(11) 691 >100 (10) −(18) 692 >100 (35) >1000 (20) 693 56 >1000 (46) 694 >100 (12) −(37) 695 >100 (10) −(37) 696 >100 (37) −(35) 697 <<10 211 698 >100 (34) −(29) 699 13 −(29) 700 >100 (30)  −(0) 701 <10 459 702 <10 495 703 <<10 375 704 16 177 705 <10 147 706 <10 227 707 17 209 708 51 348 709 19 −(19) 710 >100 (33) −(30) 711 >100 (34) −(17) 712 83 713 67 89 714 16 248 716 11 −(19) 717 >100 (8)  718 <10 −(19) 719 14 431 720 42 30 721 36 −(20) 722 <10 85 723 17 380 724 <10 116 725 <10 413 726 37 624 727 52 728 100 729 30 302 730 34 634 731 17 259 732 48 733 29 186 734 29 216 735 15 1000 736 72 737 <10 523 738 11 269 739 <10 234 740 23 335 741 49 742 92 743 10 548 744 40 745 53 746 >100 (31) 747 35 759 748 85 749 12 −(41) 750 17 −(43) 751 70 −(23) 752 >100 (37) 753 >100 (28)  −(9) 754 >100 (7)  755 >100 (3)  757 >100 (45) 758 >100 (18) 759 26 323 760 83 −(48) 761 >100 (37) −(44) 762 >100 763 13 −(39) 764 14 −(19) 765 21 937 766 >100 (45) 772 >100 (13) 550 773 >100 774 >100 (17) 775 >100 (22) 776 17 386 777 11 11 778 6 84 779 <10 107 780 6 48 781 47 135 782 14 365 783 42 451 784 6 80 785 19 71 786 5 46 787 16 37 788 11 122 789 13 154 790 <3 107 791 3 208 792 6 301 793 6 335 794 14 192 795 5 336 796 15 394 797 27 403 798 <10 439 799 14 1000 800 <10 30 801 13 70 802 <10 −(42) 803 13 −(20) 804 37 −(20) 805 >100 (14) −(35) 806 −(35) 807 >100 (20) −(20) 808 <10 61 809 <10 73 810 18 269 811 17 −(20) 812 12 326 813 23 402 814 47 405 815 74 180 816 73 123 817 53 195 818 43 205 819 48 212 820 44 187 821 39 184 822 17 451 823 11 236 824 14 268 825 58 333 826 53 170 827 38 175 828 829 −(30) −(10) 830 −(23) −(10) 831 −(50) −(19) 832 −(35) −(21) 833 452 −(26) 834 −(23)  −(1) 835 161 668 836 90 −(39) 837 −(10) −(19) 838 590 −(23) 839 −(24) −(30) 840 812 −(14) 841 28 118 842 18 127 843 43 263 844 80 450 845 >100 453 846 >100 −(33) 847 >100  −(9) 848 943 849 65 760 850 65 278 851 41 75 852 20 179 853 9 102 854 40 313 855 39 399 856 25 255 857 7 195 858 17 102 859 8 130 860 11 75 861 39 132 862 47 933 863 6 31 864 23 32 865 12 121 866 7 126 867 11 191 868 26 70 869 23 80 870 17 48 871 16 43 872 7 32 873 35 69 874 >100 151 875 40 115 876 40 242 877 43 219 878 19 65 879 20 48 880 16 149 881  >30 (29) 346 882 23 −(36) 883  >30 (30) 521 884 44 −(30) 885 <3 420 886 >100 (47) −(27) 887 50 −(20) 888 12 385 889 >100 (30) −(28) 890 95 −(39) 891 7 280 892 >100 (25) −(30) 893 52 640 894 >100 (49) −(23) 895 >100 (33) −(20) 896 96 −(31) 897 8 938 898 5 637 899 62 1000 900 10 372 901 65 −(27) 902 15 299 903 22 −(34) 904 4 −(46) 905 5 −(40) 906 47 −(29) 907 <10 572 908 9 757 909 145 −(32) 910 72 −(38) 911 9 498 912 8 497 913 8 563 914 <10 299 915 9 240 916 42 −(16) 917 132 546 918 18 552 919 73 −(11) 920 12 448 921 71 −(42) 922 12 365 923 50 −(25) 924 23 440 925 35 430 926 18 −(31) 927 5 623 928 5 289 929 94 −(21) 930 <10 184 931 23 516 932 15 208 933 18 493 934 55 143 935 59 166 936 17 427 937 69 819 938 31 532 939 15 220 940 31 292 941 12 145 942 11 335 943 19 136 944 8 140 945 25 131 946 13 142 947 39 375 948 104 830 949 51 250 950 17 224 951 50 124 952 <10 317 953 143 −(32) 954 4 131 955 12 251 956 10 326 957 10 136 958 17 194 959 <10 300 960 13 629 961 32 740 962 19 −(35) 963 59 701 964 35 −(46) 965 51 −(24) 966 25 233 967 20 −(15) 968 86 −(27) 969 48 −(19) 970 16 300 971 15 523 972 7 532 973 30  −(0) 974 49 −(34) 975 26 290 976 14 788 977 37 824 978 36 −(22) 979 29 −(25) 980 70 811 981 100 −(47) 982 96 −(18) 983 40 −(39) 984 27 −(30) 985 22 −(31) 986 <30 264 987 117 −(32) 988 24 −(33) 989 14 425 990 20 481 991 19 −(20) 992 56 766 993 52 −(35) 994 27 −(47) 995 87 −(23) 996 53 −(27) 997 9 264 998 25 591 999 29 −(45) 1000 3 771 1001 <10 −(34) 1002 <10 −(16) 1003 24 628 1004 10 877 1005 28 674 1006 29 181 1007 >30 616 1008 51 357 1009 21 243 1010 >30 78 1011 44 −(20) 1012 58 −(24) 1013 61 −(22) 1014 62 −(30) 1015 62 195 1016 48 1017 48 1018 10 320 1019 22 187 1020 35 −(11) 1021 53 −(38) 1022 28 202 1023 22 116 1024 11 141 1025 15 194 1026 44 652 1027 36 161 1028 <<10 545 1029 5 126 1030 14 337 1031 10 254 1032 <10 321 1033 67 177 1034 27 378 1035 >30 −(17) 1036 57 −(29) 1037 59 558 1038 80 597 1039 26 556 1040 <<10 414 1041 12 98 1042 39 107 1043 27 449 1044 <10 136 1045 17 193 1046 38 202 1047 >100  −(7) 1048 <10 250 1049 44 1050 23 579 1051 14 418 1052 21 408 1053 30 178 1054 27 −(19) 1055 16 312 1056 34 932 1057 24 447 1058 8 −(21) 1059 >100 550 1060 39 −(30) 1061 20 136 1062 15 233 1063 27 491 1064 12 279 1065 19 566 1066 32 279 1067 70 449 1068 14 124 1069 13 189 1070 391 1071 >100 (17)  −(0) 1072 −(34) −(18) 1073 −(23) −(20) 1074 <10 289 1075 −(17) −(31) 1076 204  −(7) 1077 48 379 1078 371 −(32) 1079 196 −(25) 1080 775  −(0) 1081 −(50) −(47) 1082 573 −(15) 1083 382 −(30) 1084 306 −(30) 1085 165 −(25) 1086 −(48) −(19) 1087 566 495 1088 265 −(23) 1089 264 −(28) 1090 562 −(30) 1091 605 −(39) 1092 −(15) −(10) 1093 621 −(32) 1094 746 −(18) 1095 −(20) −(25) 1096 −(30)  −(3) 1097 687  −(8) 1098 70 −(41) 1099 18 552 1100 553 −(18) 1101 >100 (37) −(26) 1102 >100 (38) −(11) 1103 >100 (25)  −(3) 1104 77 −(23) 1105 >100 (31)  −(1) 1106 >100 (30)  −(0) 1107 >100 (46) −(24) 1108 135 962 1109 12 353 1110 16 113 1111 46 405 1112 124 −(19) 1113 785 785 1114 118 674 1115 241 −(10) 1116 156 878 1117 185 −(31) 1118 106 −(0) 1119 334 −(27) 1120 207 778 1121 7 <30 1122 >100 (48) −(26) 1123 −(43) 961 1124 >100 (22) 1125 >100 (22)  −(8) 1126 >100 (70) −(35) 1127 >100 (8)  1128 >100 (47) −(17) 1129 >100 (48) 1130 <10 547 1131 51 192 1132 <10 146 1133 <10 42 1134 169 1135 <10 239 1136 14 639 1137 28 −(38) 1138 1139 12 783 1140 >100 (22) 1141 <10 416 1142 80 1143 >100 (32) 1144 28 −(30) 1145 548 1146 23 552 1147 10 105 1148 <10 42 1149 43 150 1150 51 192 1151 <10 146 1152 <10 1000 1153 43 −(13) 1154 49 −(21) 1155 17 −(31) 1156 >100 (35) −(28) 1157 <10 1158 46 1159 >100 1160 <10 1161 <10 1162 13 1163 >100 1164 <10 1165 >100 1166 <10 1167 >100 1168 <10 1169 37 1170 <10 1171 13 1172 34 1173 >100 1174 >100 1175 37 1176 >100 1177 17 1178 78 1179 14 327 1180 <<10 480 1181 35 −(26) 1182 <10 206 1183 <10 427 1184 55 1185 13 −(26) 1186 <<10 405 1187 24 1000 1188 76 1189 26 73 1190 24 240 1191 31 193 1192 19 672 1193 <10 −(18) 1194 56 1000 1195 21 530 1196 >100 700 1197 25 219 1198 <10 247 1199 42 1000 1200 25 716 1201 <10 450 1202 50 −(15) 1203 <10 1000 1204 18 434 1206 −(27) 1207 −(16) 1208 −(22)

Pharmacological Test Example 4 Rat Carotid Balloon Injury Model

Wistar male rats (330 to 370 mg) were anesthetized with pentobarbital anesthesia, the right femoral region was incised from the rats, a Fogaty 2F catheter was inserted through the right femoral artery and was led to the left carotid artery, and abrasion was made three times with an expansion diameter of 2.5 mm.

The test compound was suspended in 1% cremophore, and the suspension was orally administered at 0.4 ml/100 g B.W. twice a day through an oral probe for rats for 2 weeks from the day before an operation. On the second week after the operation, the rats were sacrificed by either. The left carotid artery was removed and was fixed in buffered formalin. Sliced preparations embedded in paraffin were stained with HE and were subjected to image analysis for the measurement of the neointima area (I) and media area (M) in the section of injured blood vessel. I/M was calculated as an index for the evaluation of drug efficacy.

The results were as follows. in vivo (dose: 30 mg/kg) Example No I/M ratio, inhibition (%) 223 41 287 37 408 50 421 42 516 32 567  24* 590 86 614 92 615 43 622 38 647  32* 679  54* 687  17* (*dose: 10 mg/kg)

Pharmacological Test Example 5 Measurement of Inhibitory Activity Against KDR Phosphorylation

NIH 3T3 cells (Sawano A et al., Cell Growth & Differentiation, 7, 213-221 (1996)) prepared by transfection of human KDR were cultured in a DMEM medium containing 10% FBS (GIBCO BRL) within a 5% carbon dioxide incubator until 50 to 70% confluent. The harvested cells were inoculated into wells of a collagen-type one-coat 96-well flat-bottom plate, each containing the same medium, in an amount of 1.5×10⁴ per well, followed by cultivation at 37° C. overnight. The medium was then replaced by a DMEM medium containing 0.1% FBS. A solution of a test compound in dimethyl sulfoxide was added to each well, and the cultivation was carried out at 37° C. for additional one hr. A human recombinant vascular endothelial growth factor (hereinafter abbreviated to “VEGF”) was added to a concentration of 100 ng/ml, and the stimulation of cells was carried out at 37° C. for 2 min. The medium was removed, the cells were washed with phosphate buffered saline (pH 7.4), and 50 μl of a solubilization buffer (20 mM HEPES (pH 7.4), 150 mM NaCl, 0.2% Triton X-100, 10% glycerol, 5 mM sodium orthovanadylate, 5 mM disodium ethylenediaminetetraacetate, and 2 mM Na₄P₂O₇) was then added thereto. The mixture was shaken at 4° C. for 2 hr to prepare a cell extract.

An anti-phospho-tyrosine antibody (PY20; Transduction Laboratories) was immobilized on a microplate for ELISA (Maxisorp; NUNC), and the whole quantity of the cell extract was transferred to the wells, and the immobilized antibody was reacted with the phosphorylated protein at 4° C. overnight. After washing, an anti-KDR antibody (Santa Cruz) was allowed to react at room temperature for one hr, and, further, after washing, a peroxidase-labeled anti-rabbit Ig antibody (Amersham) was allowed to react at room temperature for one hr. After washing, a chromophoric substrate for peroxidase (Sumitomo Bakelite Co., Ltd.) was added thereto and was allowed to react at room temperature. After a suitable level of color development, a reaction termination solution was added to stop the reaction, and the absorbance at 450 nm was measured with a microplate reader. The KDR phosphorylation activity for each well was determined by presuming the absorbance with the addition of VEGF and without the addition of the medicament to be 100% KDR phosphorylation activity and the absorbance without the medicament and VEGF to be 0% KDR phosphorylation activity.

The concentration of the test compound was varied on several levels, the inhibition (%) of KDR phosphorylation was determined for each case, and the concentration of the test compound necessary for inhibiting 50% of KDR phosphorylation (IC₅₀) was calculated.

The results were as follows. Example No. IC₅₀ (nM) 223 38 287 >1000 408 108 421 692 516 >1000 567 >1000 590 >1000 614 47 615 37 622 >1000 647 599 679 323 687 176

Pharmacological Test Example 6 Porcine Coronary Balloon Injury Model

Edible shoats (24 to 31 kg) were anesthetized with telazol and xylazine, a balloon catheter was inserted through the femoral artery, and the descending branch in front of the heart on the left and the right rotator branch were injured under vasographing.

For 28 days from the operation, the compound of Example 679 was orally administered as a gelatin capsule at a dose 10 mg/kg twice a day. Further, only a gelatin capsule was administered as a control. In the test, each group consisted of 6 shoats.

On the 28th day from the operation, the shoats were sacrificed with pentobarbital and were perfused with buffered formalin, and the heart was then removed. Paraffin embedded preparations of the injured blood vessel portion were sliced and stained with HE, followed by image analysis to measure the intima area (IA), media area (MA), and vessel area (VA), and the fissure length (FL) and vessel perimeter (VP) of the inner elastic plate.

IA/MA and (IA/VA)/(FL/VP) were calculated as an index for the evaluation of drug efficacy.

The results were as follows. (IA/VA)/(FL/VP) Dose (mg/kg) IA/MA inhibition(%) inhibition (%) Control — — 10 36 (p < 0.05) 47 (p < 0.001)

The compounds described in the examples have the following structures. 

1. A compound represented by formula (1) or a pharmacologically acceptable salt or solvate thereof:

wherein X and Z, which may be the same or different, represent CH or N; R¹ and R², which may be the same or different, represent a hydrogen atom or C₁₋₄ alkoxy optionally substituted by a halogen atom; R³, R⁴, R⁵, and R⁶, which may be the same or different, represent a hydrogen atom; a halogen atom; C₁₋₄ alkyl optionally substituted by a halogen atom; C₁₋₄ alkoxy optionally substituted by a halogen atom; nitro; amino; or morpholyl; A represents a group selected from the group consisting of formulae (i) to (x), wherein R¹¹ and R¹², which may be the same or different, represent a hydrogen atom, C₁₋₄ alkyl optionally substituted by a halogen atom, or C₁₋₄ alkylcarbonyl optionally substituted by a halogen atom; provided that compounds wherein R³, R⁴, R⁵ and R⁶ represent a hydrogen atom and A represents group (v) wherein u is 0 (zero) and R¹⁹ represents phenyl optionally substituted by a halogen atom, C₁₋₄ alkyl, or C₁₋₄ alkoxy are excluded:

wherein i is an integer of 0 to 10, R¹³ and R¹⁴, which may be the same or different, represent a hydrogen atom; C₁₋₆ alkyl optionally substituted by a halogen atom; or phenyl optionally substituted by a halogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom, R¹³ and R¹⁴ may form a five- to seven-membered saturated or unsaturated heterocyclic ring optionally containing one or more additional hetero-atoms together with the nitrogen atom to which they are attached, and this heterocyclic ring is optionally substituted by a halogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom, or, R¹³ or R¹⁴ may form C₁₋₄ alkylene optionally substituted by a halogen atom together with R¹²;

wherein j is an integer of 0 to 3, k is an integer of 0 to 3, provided that both j and k are not 0 (zero), m is an integer of 0 to 2, carbon atoms in the following

are optionally substituted by one or more C₁₋₄ alkyl groups, which may be the same or different, optionally substituted by a halogen atom, and R¹⁵ represents a hydrogen atom; cyclic C₃₋₇ alkyl optionally substituted by a halogen atom; phenyl optionally substituted by C₁₋₆ alkyl or a halogen atom; or C₁₋₄ alkoxycarbonyl;

wherein n is 0 (zero) or 1, p is an integer of 0 to 10, and R¹⁶ and R⁷, which may be the same or different, represent a hydrogen atom; C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₄ alkylcarbonyl optionally substituted by a halogen atom; cyclic C₃₋₇ alkyl optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom; or phenyl optionally substituted by a halogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom, or R¹⁶ and R¹⁷ may form a five- to seven-membered saturated or unsaturated heterocyclic ring optionally containing one or more additional hetero-atoms together with the nitrogen atom to which they are attached, this heterocyclic ring is optionally condensed with another one or two carbocyclic or heterocyclic ring to form a ten- to twelve-membered saturated or unsaturated bicyclic carbocyclic ring or heterocyclic ring or a ten- to fifteen-membered saturated or unsaturated tricyclic carbocyclic ring or heterocyclic ring, and these heterocyclic rings are optionally substituted by an oxygen atom or C₁₋₄ alkyl optionally substituted by a halogen atom;

wherein q is 0 (zero) or 1, r is an integer of 0 to 3, s is an integer of 0 to 3, provided that both r and s are not 0 (zero), t is an integer of 0 to 2, carbon atoms in the following

are optionally substituted by one or more C₁₋₄ alkyl groups, which may be the same or different, and R¹⁸ represents a hydrogen atom; phenyl optionally substituted by a halogen atom or C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₄ alkoxycarbonyl optionally substituted by a halogen atom;

wherein u is 0 (zero) or 1, R¹⁹ represents (1) phenyl which is optionally substituted by C₁₋₁₀ alkyl optionally substituted by a halogen atom; C₁₋₁₀ alkoxy optionally substituted by a halogen atom; —NR³¹R³² wherein R³¹ and R³², which may be the same or different, represent a hydrogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano, (2) phenoxy of which the phenyl portion is optionally substituted by C₁₋₁₀ alkyl optionally substituted by a halogen atom; C₁₋₁₀ alkoxy optionally substituted by a halogen atom; —NR³¹R³² wherein R³¹ and R³² are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano, (3) cyclic C₃₋₇ alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; cyclic C₃₋₇ alkyl optionally substituted by a halogen atom; or a halogen atom, (4) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom, (5) C₁₋₁₆ alkyl, (6) C₂₋₆ alkenyl, or (7) C₂₋₆ alkynyl, wherein (5) C₁₋₁₆ alkyl, (6) C₂₋₆ alkenyl, and (7) C₂₋₆ alkynyl are optionally substituted by one or more of the following groups: (a) phenyl optionally substituted by C₁₋₁₀ alkyl optionally substituted by a halogen atom; C₁₋₁₀ alkoxy optionally substituted by a halogen atom; —NR³¹R³² wherein R³¹ and R³² are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano, (b) phenoxy of which the phenyl portion is optionally substituted by C₁₋₁₀ alkyl optionally substituted by a halogen atom; C₁₋₁₀ alkoxy optionally substituted by a halogen atom; —NR³¹R³² wherein R³¹ and R³² are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano, (c) phenylthio of which the phenyl portion is optionally substituted by C₁₋₁₀ alkyl optionally substituted by a halogen atom; C₁₋₁₀ alkoxy optionally substituted by a halogen atom; —NR³¹R³² wherein R³¹ and R³² are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano, (d) —NR³³R³⁴ wherein R³³ and R³⁴ are as defined in R¹³ and R¹⁴, (e) cyclic C₃₋₇ alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; or a halogen atom, (f) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom, (g) naphthyl, (h) cyano, (i) C₁₋₄ alkylthio optionally substituted by a halogen atom, (j) a halogen atom, or (k) alkoxycarbonyl optionally substituted by a halogen atom;

wherein R²⁰ represents (1) phenyl optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁵R³⁶ wherein R³⁵ and R³⁶, which may be the same or different, represent a hydrogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano, (2) cyclic C₃₋₇ alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom, (3) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom, (4) C₁₋₂₀ alkyl, (5) C₂₋₆ alkenyl, or (6) C₂₋₆ alkynyl, and wherein (4) C₁₋₂₀ alkyl, (5) C₂₋₆ alkenyl, and (6) C₂₋₆ alkynyl are optionally substituted by one or more of the following groups: (a) phenyl optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁵R³⁶ wherein R³⁵ and R³⁶ are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano, (b) phenoxy of which the phenyl portion is optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁵R³⁶ wherein R³⁵ and R³⁶ are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano, (c) phenylthio of which the phenyl portion is optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁵R³⁶ wherein R³⁵ and R³⁶ are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano, (d) —NR³⁷R³⁸ wherein R³⁷ and R³⁸ are as defined in R¹³ and R¹⁴, (e) cyclic C₃₋₇ alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom, (f) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom, (g) naphthyl, or (h) cyano;

wherein v is an integer of 0 to 2, R²¹ represents (1) phenyl optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁹R⁴⁰ wherein R³⁹ and R⁴⁰, which may be the same or different, represent a hydrogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano, (2) cyclic C₃₋₇ alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom, (3) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom, (4) C₁₋₂₀ alkyl, (5) C₂₋₆ alkenyl, or (6) C₂₋₆ alkynyl, and wherein (4) C₁₋₂₀ alkyl, (5) C₂₋₆ alkenyl, and (6) C₂₋₆ alkynyl are optionally substituted by one or more of the following groups: (a) phenyl optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁹R⁴⁰ wherein R³⁹ and R⁴⁰ are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano, (b) phenoxy of which the phenyl portion is optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁹R⁴⁰ wherein R³⁹ and R⁴⁰ are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano, (c) phenylthio of which the phenyl portion is optionally substituted by C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; —NR³⁹R⁴⁰ wherein R³⁹ and R⁴⁰ are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano, (d) —NR⁴¹R⁴² wherein R⁴¹ and R⁴² are as defined in R¹³ and R¹⁴, (e) cyclic C₃₋₇ alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom, (f) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, or a halogen atom, (g) naphthyl, or (h) cyano;

wherein w is an integer of 1 to 4, L represents —O—, —S(═O)y-, wherein y is an integer of 0 to 2, or —N(—R¹¹)—, M represents —O—, —C(═O)—O—, —S(═O)z-, wherein z is an integer of 0 to 2, —N(—R¹²)—, —C(═O)—N(—R¹²)—, or —C(═O)—, R²² represents a hydrogen atom; C₁₋₄ alkyl optionally substituted by a halogen atom; or phenyl optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom, C₁₋₄ alkoxy optionally substituted by a halogen atom, nitro, amino, or a halogen atom, when M represents —N(—R¹²)— or —C(═O)—N(—R¹²)—, R²² and R¹² may form a five- to seven-membered saturated or unsaturated heterocyclic ring optionally containing one or more additional hetero-atoms together with the nitrogen atom to which they are attached, this heterocyclic ring is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring, and these heterocyclic rings are optionally substituted by C₁₋₄ alkyl optionally substituted by a halogen atom; phenyl; benzyl; or piperidine; —OR²³  (ix) wherein R²³ represents a hydrogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom; and —NR²⁴R²⁵  (x) wherein R²⁴ and R²⁵, which may be the same or different, represent a hydrogen atom or C₁₋₄ alkyl optionally substituted by a halogen atom.
 2. The compound according to claim 1, wherein X represents CH or N and Z represents CH.
 3. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy and at least one of R³, R⁴, R⁵, and R⁶ represents a group other than a hydrogen atom.
 4. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy, R³ represents a group other than a hydrogen atom, and R⁴, R⁵, and R⁶ represent a hydrogen atom.
 5. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (i) wherein i is an integer of 1 to 3; and R¹³ and R⁴, which may be the same or different, represent C₁₋₄ alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl together with the nitrogen atom to which they are attached.
 6. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy, R³, R⁴, R⁵, and R⁶ represent a hydrogen atom, and A represents group (i) wherein i is an integer of 1 to 3 and R¹³ and R⁴, which may be the same or different, represent C₁₋₄ alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl together with the nitrogen atom to which they are attached.
 7. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy, R³ represents a group other than a hydrogen atom, R⁴, R⁵, and R⁶ represent a hydrogen atom, and A represents group (i) wherein i is an integer of 1 to 3 and R¹³ and R¹⁴, which may be the same or different, represent C₁₋₄ alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl together with the nitrogen atom to which they are attached.
 8. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy, R³ represents nitro, R⁴, R⁵, and R⁶ represent a hydrogen atom, and A represents group (i) wherein i is an integer of 1 to 3 and R¹³ and R¹⁴, which may be the same or different, represent C₁₋₄ alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl together with the nitrogen atom to which they are attached.
 9. The compound according to claim 1, wherein X represents N, Z represents CH, R¹ and R² represent C₁₋₄ alkoxy, R³ represents nitro, R⁴, R⁵, and R⁶ represent a hydrogen atom, and A represents group (i) wherein i is an integer of 1 to 3 and R¹³ and R¹⁴, which may be the same or different, represent C₁₋₄ alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl together with the nitrogen atom to which they are attached.
 10. The compound according to claim 1, wherein X represents N, Z represents CH, R¹ and R² represent C₁₋₄ alkoxy, R³ represents nitro, R⁴, R⁵, and R⁶ represent a hydrogen atom, and A represents group (i) wherein i is 2 and R¹³ and R¹⁴, which may be the same or different, represent C₂₋₃ alkyl, or may form a six-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl together with the nitrogen atom to which they are attached.
 11. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (ii) wherein j is 1 or 2, k is 1 or 2, m is 1 or 2, and R¹⁵ represents optionally substituted phenyl.
 12. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy, R³, R⁴, R⁵, and R⁶ represent a hydrogen atom, and A represents group (ii) wherein j is 1 or 2, k is 1 or 2, m is 1 or 2, and R¹⁵ represents optionally substituted phenyl.
 13. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy, R³ represents a group other than a hydrogen atom, R⁴, R⁵, and R⁶ represent a hydrogen atom, and A represents group (ii) wherein j is 1 or 2, k is 1 or 2, m is 1 or 2, and R¹⁵ represents optionally substituted phenyl.
 14. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (iii) wherein n is 0 (zero); p is an integer of 1 to 3; and R¹⁶ and R¹⁷, which may be the same or different, represent C₁₋₄ alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl or an oxygen atom together with the nitrogen atom to which they are attached.
 15. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy, R³, R⁴, R⁵ and R⁶ represent a hydrogen atom, and A represents group (iii) wherein n is 0 (zero); p is an integer of 1 to 3; and R¹⁶ and R⁷, which may be the same or different, represent C₁₋₄ alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl or an oxygen atom together with the nitrogen atom to which they are attached.
 16. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy, R³ represents a group other than a hydrogen atom, R⁴, R⁵ and R⁶ represent a hydrogen atom, and A represents group (iii) wherein n is 0 (zero), p is an integer of 1 to 3, and R¹⁶ and R¹⁷, which may be the same or different, represent C₁₋₄ alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C₁₋₄ alkyl or an oxygen atom together with the nitrogen atom to which they are attached.
 17. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (iv) wherein q is 0 (zero), r is 1 or 2, s is 1 or 2, t is 1 or 2, and R¹⁸ represents optionally substituted phenyl.
 18. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy, R³, R⁴, R⁵ and R⁶ represent a hydrogen atom, and A represents group (iv) wherein q is 0 (zero), r is 1 or 2, s is 1 or 2, t is 1 or 2, and R¹⁸ represents optionally substituted phenyl.
 19. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy, R³ represents a group other than a hydrogen atom, R⁴, R⁵, and R⁶ represent a hydrogen atom, and A represents group (iv) wherein q is 0 (zero), r is 1 or 2, s is 1 or 2, t is 1 or 2, and R¹⁸ represents optionally substituted phenyl.
 20. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (v) wherein u is 1 and R¹⁹ represents optionally substituted phenyl, or C₁₋₄ alkyl substituted by optionally substituted phenyl.
 21. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy, R³, R⁴, R⁵, and R⁶ represent a hydrogen atom, and A represents group (v) wherein u is 1 and R¹⁹ represents optionally substituted phenyl, or C₁₋₄ alkyl substituted by optionally substituted phenyl.
 22. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy, R⁵ represents a group other than a hydrogen atom, R³, R⁴, and R⁶ represent a hydrogen atom, and A represents group (v) wherein u is 1 and R¹⁹ represents optionally substituted phenyl, or C₁₋₄ alkyl substituted by optionally substituted phenyl.
 23. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (vi) wherein R²⁰ represents optionally substituted phenyl, or C₁₋₆ alkyl optionally substituted by optionally substituted phenyl.
 24. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (vii) wherein R²¹ represents optionally substituted phenyl, or C₁₋₆ alkyl optionally substituted by optionally substituted phenyl.
 25. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (viii) wherein w is an integer of 1 to 3, L represents —O—, M represents —O— or —C(═O)—O—, and R²² represents optionally substituted phenyl.
 26. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (viii) wherein, when L represents —O—, M represents —O—, —C(═O)—O—, —N(—R¹²)—, —C(═O)—N(—R¹²)—, or —C(═O)—; when L represents —S(═O)y-, M represents —O—; and, when L represents —N(—R¹¹)—, M represents —O—.
 27. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy and A represents group (iii) wherein n is 1 and p is 0 (zero).
 28. The compound according to claim 1, wherein R¹ and R² represent C₁₋₄ alkoxy, R³ represents morpholyl, R⁴, R⁵, and R⁶ represent a hydrogen atom, and A represents group (x).
 29. A compound selected from the group consisting of the following compounds or pharmacologically acceptable salts or solvates thereof: N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}-N′-(2-piperidinoethyl)urea; and N-[2-(diethylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}urea.
 30. A pharmaceutical composition comprising the compound according to claim 1 or a pharmacologically acceptable salt or solvate thereof.
 31. The pharmaceutical composition according to claim 30, which contains an amount of said compound effective to treat a disease mediated by the autophosphorylation of a PDGF receptor.
 32. The pharmaceutical composition according to claim 31, wherein the disease mediated by the autophosphorylation of the PDGF receptor is selected from the group consisting of ischemic diseases involving blood vessel occlusion or angiostenosis induced by angiopathy; ischemic diseases involving blood vessel occlusion or angiostenosis induced by vascular autotransplantation or allotransplantation; and diseases involving cell proliferation and organ fibrosis induced by PDGF, including chronic rheumatism, PDGF-dependent tumors such as glioma, cirrhosis, pulmonary fibrosis, and occlusion of arteriovenous shunt.
 33. The pharmaceutical composition according to claim 30, which contains an amount of said compound effective to inhibit angiostenosis. 